WorldWideScience

Sample records for 6-ohda rat model

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

    Science.gov (United States)

    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. Protective effects of neurotrophic factor-secreting cells in a 6-OHDA rat model of Parkinson disease.

    Science.gov (United States)

    Sadan, Ofer; Bahat-Stromza, Merav; Barhum, Yael; Levy, Yossef S; Pisnevsky, Anat; Peretz, Hagit; Ilan, Avihay Bar; Bulvik, Shlomo; Shemesh, Noam; Krepel, Dana; Cohen, Yoram; Melamed, Eldad; Offen, Daniel

    2009-10-01

    Stem cell-based therapy is a promising treatment for neurodegenerative diseases. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells (MSC) into neurotrophic factors- secreting cells (NTF-SC), thus combining stem cell-based therapy with the NTF-based neuroprotection. These cells produce and secrete factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor. Conditioned medium of the NTF-SC that was applied to a neuroblastoma cell line (SH-SY5Y) 1 h before exposure to the neurotoxin 6-hydroxydopamine (6-OHDA) demonstrated marked protection. An efficacy study was conducted on the 6-OHDA-induced lesion, a rat model of Parkinson's disease. The cells, either MSC or NTF-SC, were transplanted on the day of 6-OHDA administration and amphetamine-induced rotations were measured as a primary behavior index. We demonstrated that when transplanted posterior to the 6-OHDA lesion, the NTF-SC ameliorated amphetamine-induced rotations by 45%. HPLC analysis demonstrated that 6-OHDA induced dopamine depletion to a level of 21% compared to the untreated striatum. NTF-SC inhibited dopamine depletion to a level of 72% of the contralateral striatum. Moreover, an MRI study conducted with iron-labeled cells, followed by histological verification, revealed that the engrafted cells migrated toward the lesion. In a histological assessment, we found that the cells induced regeneration in the damaged striatal dopaminergic nerve terminal network. We therefore conclude that the induced MSC have a therapeutic potential for neurodegenerative processes and diseases, both by the NTFs secretion and by the migratory trait toward the diseased tissue.

  3. Antioxidant effect of Spirulina (Arthrospira) maxima in a neurotoxic model caused by 6-OHDA in the rat striatum.

    Science.gov (United States)

    Tobón-Velasco, J C; Palafox-Sánchez, Victoria; Mendieta, Liliana; García, E; Santamaría, A; Chamorro-Cevallos, G; Limón, I Daniel

    2013-08-01

    There is evidence to support that an impaired energy metabolism and the excessive generation of reactive oxygen species (ROS) contribute to brain injury in neurodegenerative disorders such as Parkinson's disease (PD), whereas diets enriched in foods with an antioxidant action may modulate its progression. Several studies have proved that the antioxidant components produced by Spirulina, a microscopic blue-green alga, might prevent cell death by decreasing free radicals, inhibiting lipoperoxidation and upregulating the antioxidant enzyme systems. In our study, we investigated the protective effect of the Spirulina maxima (S. maxima) against the 6-OHDA-caused toxicity in the rat striatum. The S. maxima (700 mg/kg/day, vo) was administered for 40 days before and 20 days after a single injection of 6-OHDA (16 μg/2 μL) into the dorsal striatum. At 20-day postsurgery, the brain was removed and the striatum was obtained to evaluate the indicators of toxicity, such as nitric oxide levels, ROS formation, lipoperoxidation, and mitochondrial activity. These variables were found significantly stimulated in 6-OHDA-treated rats and were accompanied by declines in dopamine levels and motor activity. In contrast, the animals that received the chronic treatment with S. maxima had a restored locomotor activity, which is associated with the decreased levels of nitric oxide, ROS, and lipoperoxidation in the striatum, although mitochondrial functions and dopamine levels remained preserved. These findings suggest that supplementation with antioxidant phytochemicals (such as contained in S. maxima) represents an effective neuroprotective strategy against 6-OHDA-caused neurotoxicity vía free radical production to preserve striatal dopaminergic neurotransmission in vivo.

  4. Neurodegenerative Shielding by Curcumin and Its Derivatives on Brain Lesions Induced by 6-OHDA Model of Parkinson's Disease in Albino Wistar Rats

    Directory of Open Access Journals (Sweden)

    Shyam Sunder Agrawal

    2012-01-01

    Full Text Available Study was undertaken to evaluate the neurodegenerative defending potential of curcumin (CUR, demethoxycurcumin (DMC, and bisdemethoxycurcumin (BDMC on 6-hydroxydopamine-(6-OHDA induced Parkinsonism model in rats. Curcuminoids were administered (60 mg/kg, body weight, per oral for three weeks followed by unilateral injection of 6-OHDA on 22nd day (10 μg/2 μL into the right striatum leading to extensive loss of dopaminergic cells. The behavioral observations, biochemical markers, quantification of dopamine (DA, DOPAC, and HVA followed by dopamine (D2 receptor binding assay and tyrosine hydroxylase (TH, using immunohistochemistry were evaluated using HPLC after three weeks of lesion. Pretreated animals showed significant protection against neuronal degeneration compared to lesion animals by normalizing the deranged levels of biomarkers and showed the potency in the order CUR > DMC > BDMC. The same order of effectiveness was observed in D2 receptors binding assay and TH immunohistochemistry study. We conclude that curcuminoids appear to shield progressive neuronal degeneration from increased oxidative attack in 6-OHDA-lesioned rats through its free radical scavenging mechanism, and DA, DOPAC, and HVA enhancing capabilities in the sequence of efficacy CUR > DMC > BDMC. Further, curcuminoids may have potential utility in treatment of many more oxidative stress-induced neurodegenerative disorders.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  7. 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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

    OpenAIRE

    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. Protective Effect of GSH on PD Model Induced by 6-OHDA In Vitro

    Institute of Scientific and Technical Information of China (English)

    徐岩; 孙圣刚; 曹学兵; 童萼塘

    2002-01-01

    Summary: To study the effects of 6-hydroxydopamine (6-OHDA) and reduced glutathione (GSH)on the nigral dopaminergic neurons in brain slices in vitro, immolunohistochemical technique wasused to observe the changes of TH-stained neurons, including cell bodies and the dendrites, in thesubstantia nigra (SN) of midbrain slices of rats after incubation for 1 h in the presence of GSH 15min before and during the period of incubation with 6-OHDA. The results showed that cell bodiesremained intact but dendrites were fragmented and truncated after treatment with 6-OHDA. Theantioxidant GSH alone did not significantly affect the dendrites of SN neurons but prevented 6-O-HDA-induced damage of dendrites. It was concluded that glutathione may prevent 6-OHDA-in-duced dopaminergic neurodegeneration and play a protective role in dopaminergic neurons.

  13. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Matheus, Filipe C; Rial, Daniel; Real, Joana I; Lemos, Cristina; Ben, Juliana; Guaita, Gisele O; Pita, Inês R; Sequeira, Ana C; Pereira, Frederico C; Walz, Roger; Takahashi, Reinaldo N; Bertoglio, Leandro J; Da Cunha, Cláudio; Cunha, Rodrigo A; Prediger, Rui D

    2016-03-15

    Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.

  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

    Institute of Scientific and Technical Information of China (English)

    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.

    Science.gov (United States)

    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. Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Andereggen, Lukas; Meyer, Morten; Guzman, Raphael;

    2009-01-01

    Transplantation of fetal dopaminergic (DA) neurons offers an experimental therapy for Parkinson's disease (PD). The low availability and the poor survival and integration of transplanted cells in the host brain are major obstacles in this approach. Glial cell line-derived neurotrophic factor (GDNF......) is a potent neurotrophic factor with growth- and survival-promoting capabilities for developing DA neurons. In the present study, we examined whether pretreatment of ventral mesencephalic (VM) free-floating roller tube (FFRT) cultures with GDNF would improve graft survival and function. For that purpose...... organotypic cultures of E14 rat VM were grown for 2, 4 or 8 days in the absence (control) or presence of GDNF [10 ng/ml] and transplanted into the striatum of 6-hydroxydopamine-lesioned rats. While all groups of rats showed a significant reduction in d-amphetamine-induced rotations at 6 weeks...

  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

    Institute of Scientific and Technical Information of China (English)

    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

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

    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.

    Science.gov (United States)

    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

    Directory of Open Access Journals (Sweden)

    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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    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

  4. Neuroprotective effects of aqueous extracts of Uncaria tomentosa: Insights from 6-OHDA induced cell damage and transgenic Caenorhabditis elegans model.

    Science.gov (United States)

    Shi, Zhenhua; Lu, Zhongbing; Zhao, Yashuo; Wang, Yueqi; Zhao-Wilson, Xi; Guan, Peng; Duan, Xianglin; Chang, Yan-Zhong; Zhao, Baolu

    2013-06-01

    Previous pharmacological studies have indicated that AC11 (a standardized aqueous extract of Uncaria tomentosa) has beneficial effects on DNA repair and immune function. However, its benefits go beyond this. The present study utilized electron spin resonance (ESR) and spin trapping technique, as well as the 6-OHDA-induced cell damage and transgenic Caenorhabditis elegans models, towards exploring the antioxidant and neuroprotective ability of AC11. Our results showed that AC11 could scavenge several types of free radicals, especially hydroxyl radicals (60% of hydroxyl radicals were scavenged by 30 μg/ml of AC11). In SH-SY5Y cells, we found that AC11 could dose dependently protect 6-OHDA induced cell damage by increase cell viability and mitochondrial membrane potential. AC11 pretreatment also significantly decreased the level of lipid peroxidation, intracellular reactive oxygen species and nitric oxide in 6-OHDA treated cells. In NL5901 C. elegans, 10 μg/ml AC11 could reduce the aggregation of α-synuclein by 40%. These findings encourage further investigation on AC11 and its active constituent compounds, as possible therapeutic intervention against Parkinson's disease.

  5. The CB1 cannabinoid receptor agonist reduces L-DOPA-induced motor fluctuation and ERK1/2 phosphorylation in 6-OHDA-lesioned rats.

    Science.gov (United States)

    Song, Lu; Yang, Xinxin; Ma, Yaping; Wu, Na; Liu, Zhenguo

    2014-01-01

    The dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) has been used as an effective drug for treating dopamine depletion-induced Parkinson's disease (PD). However, long-term administration of L-DOPA produces motor complications. L-DOPA has also been found to modify the two key signaling cascades, protein kinase A/dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), in striatal neurons, which are thought to play a pivotal role in forming motor complications. In the present study, we tested the possible effect of a CB1 cannabinoid receptor agonist on L-DOPA-stimulated abnormal behavioral and signaling responses in vivo. Intermittent L-DOPA administration for 3 weeks induced motor fluctuation in a rat model of PD induced by intrastriatal infusion of dopamine-depleting neurotoxin 6-hydroxydopamine (6-OHDA). A single injection of a CB1 cannabinoid receptor agonist WIN-55,212-2 had no effect on L-DOPA-induced motor fluctuation. However, chronic injections of WIN-55,212-2 significantly attenuated abnormal behavioral responses to L-DOPA in 6-OHDA-lesioned rats. Similarly, chronic injections of WIN-55,212-2 influence the L-DOPA-induced alteration of DARPP-32 and ERK1/2 phosphorylation status in striatal neurons. These data provide evidence for the active involvement of CB1 cannabinoid receptors in the regulation of L-DOPA action during PD therapy.

  6. Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC{delta} in cell culture and animal models of Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi, E-mail: arthik@iastate.edu

    2011-11-15

    The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 {mu}M) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 {mu}M) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKC{delta}) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 {mu}M). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKC{delta}{sup D327A} and kinase dead PKC{delta}{sup K376R} or siRNA-mediated knockdown of PKC{delta} protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKC{delta} promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKC{delta} expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKC{delta} cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKC{delta}{sup D327A} protein protected against 6-OHDA-induced PKC{delta} activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKC{delta} is a key downstream event in dopaminergic degeneration, and these results may have important translational value for

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

    NARCIS (Netherlands)

    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

  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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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 < 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.

  11. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats.

    Science.gov (United States)

    Cai, Jingli; Yang, Ming; Poremsky, Elizabeth; Kidd, Sarah; Schneider, Jay S; Iacovitti, Lorraine

    2010-07-01

    Cell replacement therapy could be an important treatment strategy for Parkinson's disease (PD), which is caused by the degeneration of dopamine neurons in the midbrain (mDA). The success of this approach greatly relies on the discovery of an abundant source of cells capable of mDAergic function in the brain. With the paucity of available human fetal tissue, efforts have increasingly focused on renewable stem cells. Human induced pluripotent stem (hiPS) cells offer great promise in this regard. If hiPS cells can be differentiated into authentic mDA neuron, hiPS could provide a potential autologous source of transplant tissue when generated from PD patients, a clear advantage over human embryonic stem (hES) cells. Here, we report that mDA neurons can be derived from a commercially available hiPS cell line, IMR90 clone 4, using a modified hES differentiation protocol established in our lab. These cells express all the markers (Lmx1a, Aldh1a1, TH, TrkB), follow the same mDA lineage pathway as H9 hES cells, and have similar expression levels of DA and DOPAC. Moreover, when hiPS mDA progenitor cells are transplanted into 6-OHDA-lesioned PD rats, they survive long term and many develop into bona fide mDA neurons. Despite their differentiation and integration into the brain, many Nestin+ tumor-like cells remain at the site of the graft. Our data suggest that as with hES cells, selecting the appropriate population of mDA lineage cells and eliminating actively dividing hiPS cells before transplantation will be critical for the future success of hiPS cell replacement therapy in PD patients.

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

    Science.gov (United States)

    Sgroi, Stefania; Kaelin-Lang, Alain; Capper-Loup, Christine

    2014-01-01

    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. PMID:25324746

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

    Directory of Open Access Journals (Sweden)

    Stefania eSgroi

    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.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...... challenge. Unilateral lesions were associated with a more distinct increase in [(3)H]NPA binding ex vivo than was seen for [(3)H]raclopride binding in vitro. Furthermore, this preferential asymmetry in [(3)H]NPA binding was more pronounced in amphetamine treated rats. We consequently predict that agonist...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...... ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  20. Behavioral and biochemical correlates of the dyskinetic potential of dopaminergic agonists in the 6-OHDA lesioned rat.

    Science.gov (United States)

    Carta, Anna R; Frau, Lucia; Lucia, Frau; Pinna, Annalisa; Annalisa, Pinna; Pontis, Silvia; Silvia, Pontis; Simola, Nicola; Nicola, Simola; Schintu, Nicoletta; Nicoletta, Schintu; Morelli, Micaela; Micaela, Morelli

    2008-07-01

    Prolonged treatment with L-DOPA induces highly disabling dyskinesia in Parkinson's disease (PD) patients. In contrast, dopaminergic agonists display variably dyskinetic outcome, depending on pharmacokinetic/pharmacodynamic profile. The present study was aimed at assessing behavioral and biochemical correlates of intense or mild dyskinesia displayed by the different dopamine (DA) receptors stimulation in a rat model of PD. The effect of subchronic stimulation of the D(1) receptor by SKF38393, and the D(2)/D(3) receptor by ropinirole was evaluated in unilaterally 6-hydroxyDA-lesioned rats. Sensitization of contralateral turning (SCT) behavior and abnormal involuntary movements (AIMs) were assessed as behavioral correlates of dyskinetic responses. Opioid peptides mRNA in the dorsolateral striatum (dlStr) and glutamic acid decarboxylase (GAD67) mRNA content in globus pallidus (GP), were evaluated as an index of neuroadaptive changes occurring in the direct and indirect basal ganglia pathways. Subchronic SKF38393 caused AIMs and SCT whereas ropinirole elicited SCT only, indicating that both drugs induced some dyskinetic response, albeit of different type. Peptides mRNA evaluation in dlStr, showed that SKF38393 subchronic treatment was associated to an overexpression of both dynorphin (DYN) and enkephalin (ENK) mRNAs, in the direct and indirect striatal pathway respectively. In contrast, a decrease in DYN mRNA levels only was observed after treatment with ropinirole. Analysis of GAD67 mRNA levels in the GP showed an increase after both D(1) and D(2)/D(3) agonist treatments. Results suggest that presence of SCT alone or SCT plus AIMs might represent correlates of the differential severity of dyskinetic movements induced by treatment with low (ropinirole) or high (SKF38393) dyskinetic potential. Neuroadaptive increases in opioid peptide expression in both direct and indirect striatal pathways were associated to the appearance of AIMs alone. In contrast, increase of GAD67 m

  1. Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

    DEFF Research Database (Denmark)

    Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N;

    2016-01-01

    UNLABELLED: Increasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response in PD seems to involve, not only microglia, but also other immune cells infiltrated into the brain. Indeed, we observed here the infiltration...... of macrophages, specifically CD163+ macrophages, into the area of neurodegeneration in the 6-hydroxydopamine (6-OHDA) PD model. Therefore, we investigated the therapeutic potential of the infiltrated CD163+ macrophages to modulate local microglia in the brain to achieve neuroprotection. To do so, we designed...... intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia...

  2. The effects of Nanog gene transfer on NF-κB expression in rats with Parkinson's disease induced by 6-OHDA%转Nanog基因对6-羟基多巴胺帕金森病大鼠脑核因子-κB表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈施艳; 冯飞阳; 张志坚; 周海涛; 吴秀丽

    2014-01-01

    目的:探讨转Nanog基因对6-羟多巴胺(6-OHDA)诱导的帕金森病(PD)大鼠A脑内核因子(NF)-κB表达的影响。方法取SD大鼠随机分成正常对照组、6-OHDA+磷酸盐缓冲液( PBS)组、6-OHDA+PNL组与6-OHDA+Nanog组,各组又分注射后1、14 d亚组。除正常对照组外,采用脑立体定向注射技术,6-OHDA+PBS组注入PBS,6-OHDA+PNL组注入空载体,6-OHDA+Nanog组注入转Nanog基因载体。各组动物注射阿朴吗啡(APO)后观察各时间点大鼠的旋转行为改变;行脑免疫组织化学染色,观察黑质多巴胺(DA)能神经元数量变化、纹状体NF-κBp65的表达改变;激光扫描共聚焦显微镜技术检测NF-κBp65表达的定位。结果注射后14 d,6-OHDA+Nanog组大鼠APO诱发的旋转效应明显低于6-OHDA+PNL组与6-OHDA+PBS组(P<0.05);除正常对照组外,其他各组大鼠注射后14 d黑质TH阳性细胞数普遍较注射后1 d减少(P<0.01),但6-OHDA+Nanog组损毁侧黑质存活的TH阳性细胞数明显高于6-OHDA+PNL组与6-OHDA+PBS组(P<0.01),且其注射侧纹状体 NF-κBp65阳性细胞数低于注射后1 d组(P<0.05)、注射后14 d的6-OHDA+PNL与6-OHDA+PBS组(P<0.05)。除正常对照组外,注射后各组各时程均可见 NF-κBp65的阳性表达,并呈现核内转移现象。结论转Nanog基因可抑制6-OHDA诱导的PD大鼠模型脑内NF-κB的活化,同时具有神经元保护作用。%Objective To observe the effects of Nanog on NF-κB expression in Parkinson's disease ( PD) model.Methods SD rats were randomly divided into control ,6-OHDA+PBS,6-OHDA+PNL and 6-OHDA+Nanog groups.Rats were given a brain injection of phos-phate buffered saline (PBS), PLNCX (PLN) and Nanog gene vector respectively , and were divided into post injection 1 st, 14 th day sub-groups.The Apomorphine ( APO) was injected in each

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  9. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  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

    Institute of Scientific and Technical Information of China (English)

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  15. Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2015-01-01

    Full Text Available Resveratrol, herbal nonflavonoid polyphenolic compound naturally derived from grapes, has long been acknowledged to possess extensive biological and pharmacological properties including antioxidant and anti-inflammatory ones and may exert a neuroprotective effect on neuronal damage in neurodegenerative diseases. However, the underlying molecular mechanisms remain undefined. In the present study, we intended to investigate the neuroprotective effects of resveratrol against 6-OHDA-induced neurotoxicity of PC12 cells and further explore the possible mechanisms involved. For this purpose, PC12 cells were exposed to 6-OHDA in the presence of resveratrol (0, 12.5, 25, and 50 μM. The results showed that resveratrol increased cell viability, alleviated the MMP reduction, and reduced the number of apoptotic cells as measured by MTT assay, JC-1 staining, and Hoechst/PI double staining (all p<0.01. Immunofluorescent staining and Western blotting revealed that resveratrol averts 6-OHDA induced CXCR4 upregulation (p<0.01. Our results demonstrated that resveratrol could effectively protect PC12 cells from 6-OHDA-induced oxidative stress and apoptosis via CXCR4 signaling pathway.

  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

    Institute of Scientific and Technical Information of China (English)

    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.

    Science.gov (United States)

    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. Neurokinin receptor 3 peptide exacerbates 6-hydroxydopamine-induced dopaminergic degeneration in rats through JNK pathway.

    Science.gov (United States)

    Chu, John Man Tak; Chan, Ying Shing; Chen, Liang Wei; Yung, Ken Kin Lam

    2012-11-01

    Neurokinin 3 (NK3) receptor is predominantly expressed in striatum and substantia nigra (SN). Evidences have indicated the roles of NK3 receptor in the pathogenesis of Parkinson's disease. By administrating NK3 receptor agonist senktide into 6-hydroxydopamine (6-OHDA)-lesioned rats, exacerbation of dopaminergic degeneration was found in striatum and substantia nigra pars compacta. From apomorphine rotation test, significant increase of contralateral rotation number was detected in 6-OHDA-lesioned rats with senktide injection. Furthermore, tyrosine hydroxylase expression in striatum and substantia nigra pars compacta were examined by immunohistochemistry and Western blotting. Further reduction of tyrosine hydroxylase immunoreactivities was found in 6-OHDA-lesioned rats that received senktide treatment. Also, phosphorylation of N-methyl-D-aspartate receptor 1 subunit was investigated in SN region and significant up-regulation was revealed in senktide-treated 6-OHDA-lesioned rats. Finally, phosphorylation of mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and c-Jun were examined in nigral region. Up-regulation of phosphorylated JNK molecules was shown in SN region after senktide injection. In line with this evidence, phosphorylation of c-Jun at Ser 63 and Ser 73 was also up-regulated by senktide treatment, thus presenting new aspects that NK3 peptide could exacerbate 6-OHDA toxicity in in vivo models and the possible mechanism may be contributed by the modulation of N-methyl-D-aspartate receptor 1 subunit and JNK pathway activities.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Effects of 6-OHDA lesion of hippocampal CA3 dopaminergic system on conditioned fear memory in rats%损毁海马CA3区多巴胺能系统对大鼠条件性恐惧记忆的影响

    Institute of Scientific and Technical Information of China (English)

    文加玲; 时燕薇; 赵虎

    2012-01-01

    目的 研究大鼠海马CA3区多巴胺(DA)能系统在条件性恐惧记忆形成与保持中的作用.方法 条件性恐惧训练前2周向双侧海马CA3区注入6-羟基多巴胺(6-OHDA)进行损毁,训练后用Western blotting检测前额叶皮层、CA1、杏仁体GluR1及NR2B的表达变化.结果 (1)与生理盐水组[(66.44±16.58)%,(73.43±23.57)%,(55.27±20.57)%]比较,6-OHDA损毁组恐惧记忆获得的僵住反应[ (65.58±5.33)%]差异无统计学意义(P>0.05),短时恐惧记忆的僵住反应[(39.24±12.83)%]与长时恐惧记忆的僵住反应[(31.15±6.51)%]明显减少(P<0.05).(2)与生理盐水组比较,6-OHDA损毁组大鼠前额叶皮层,海马CA1区的GluR1蛋白表达差异无统计学意义(P>0.05),杏仁体BLA区的GluR1蛋白表达升高(P<0.01).与生理盐水组比较,6-OHDA损毁组大鼠前额叶皮层的NR2B蛋白表达升高(P<0.01),海马CA1区的NR2B蛋白表达差异无统计学意义(P>0.05),杏仁体BLA区的NR2B蛋白表达降低(P<0.01).结论 大鼠海马CA3区多巴胺能系统功能下调能损害恐惧记忆的巩固但不影响其获得,还可以调节其他脑区记忆相关蛋白的表达.%Objective To investigate the effects of hippocampal CA3 dopaminergic system in acquisition and consolidation of Pavlovian fear conditioning,and expression of GluR1 and NR2B in medial prefrontal cortex (mPFC),CA1 and basolateral amygdala (BLA) after fear conditioning training.Methods Bilateral injection 6-OHDA into hippocampal CA3 to lesion dopaminergic fibers 2 weeks before fear conditioning training.The change of GluR1 and NR2B were analyzed by western blot after training.Results Compared with the saline group ( (66.44 ± 16.58)% ),there were significant decreases ( (39.24 ± 12.83)%,(31.15 ±6.51 )% ) in the consolidation of short- and long- term fear memory (P < 0.05 ) but not the acquisition ( ( 65.58 ± 5.33 ) %,P > 0.05).The expression of GluR1 protein was significantly increased in BLA

  2. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

    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

  6. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson's Disease

    Science.gov (United States)

    Wang, Bing; Chen, Li-Hua

    2016-01-01

    In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain. PMID:27747105

  7. 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

    Directory of Open Access Journals (Sweden)

    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.

  8. 6-OHDA lesions to amygdala and hippocampus attenuate memory-enhancing effect of the 3-7 fragment of angiotensin II.

    Science.gov (United States)

    Winnicka, M M; Braszko, J J; Wiśniewski, K

    1998-05-01

    We have previously shown that facilitatory effect of angiotensin II (AII) on the retrieval of memory is mediated by the dopaminergic system. In the present study, we searched for the influence of the 3-7 fragment of angiotensin II [AII(3-7)] on the retrieval processes in a passive avoidance situation after bilateral 6-OHDA lesions to the central amygdala (CA) and the CA4 field of the hippocampus (HI). AII(3-7) given 15 min before the retention testing, at the intracerebroventricular dose of 1 nmol, significantly prolonged avoidance latencies in sham-operated rats (i.e. improved retrieval of memory for the electric footshock experienced during the learning trial). Bilateral lesions to CA totally abolished, and to HI significantly diminished, this facilitatory effect. An increase of spontaneous locomotor activity in rats lesioned to CA and a decrease in rats lesioned to HI were unlikely to interfere with the cognitive effect of AII (3-7). These results suggest that the anatomical substrate of facilitating retrieval of information activity of AII(3-7) is closely related to the dopaminergic projection from the ventral tegmental area and substantia nigra to CA and HI.

  9. Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Chien-Wei Feng

    2016-10-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH, a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies.

  10. Neuroprotective Effect of the Marine-Derived Compound 11-Dehydrosinulariolide through DJ-1-Related Pathway in In Vitro and In Vivo Models of Parkinson’s Disease

    Science.gov (United States)

    Feng, Chien-Wei; Hung, Han-Chun; Huang, Shi-Ying; Chen, Chun-Hong; Chen, Yun-Ru; Chen, Chun-Yu; Yang, San-Nan; Wang, Hui-Min David; Sung, Ping-Jyun; Sheu, Jyh-Horng; Tsui, Kuan-Hao; Chen, Wu-Fu; Wen, Zhi-Hong

    2016-01-01

    Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH), a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies. PMID:27763504

  11. Restoring Spinal Noradrenergic Inhibitory Tone Attenuates Pain Hypersensitivity in a Rat Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Lei-Fang Cao

    2016-01-01

    Full Text Available In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA into the bilateral striatum (CPu. PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4 aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE precursor droxidopa (L-DOPS or α2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE and 5-hydroxytryptamine (5-HT reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson's disease.

    Science.gov (United States)

    Jia, Yu; Mo, Shi-Jing; Feng, Qi-Qi; Zhan, Ma-Li; OuYang, Li-Si; Chen, Jia-Chang; Ma, Yu-Xin; Wu, Jia-Jia; Lei, Wan-Long

    2014-05-01

    Erythropoietin (EPO) may become a potential therapeutic candidate for the treatment of the neurodegenerative disorder -- Parkinson's disease (PD), since EPO has been found to prevent neuron apoptosis through the activation of cell survival signalling. However, the underlying mechanisms of how EPO exerts its neuroprotective effect are not fully elucidated. Here we investigated the mechanism by which EPO suppressed 6-hydroxydopamine (6-OHDA)-induced neuron death in in vitro and in vivo models of PD. EPO knockdown conferred 6-OHDA-induced cytotoxicity. This effect was reversed by EPO administration. Treatment of PC12 cells with EPO greatly diminished the toxicity induced by 6-OHDA in a dose- and time-dependent manner. EPO effectively reduced apoptosis of striatal neurons and induced a significant improvement on the neurological function score in the rat models of PD. Furthermore, EPO increased the expression of phosphorylated Akt and phosphorylated FoxO3a, and abrogated the 6-OHDA-induced dysregulation of Bcl-2, Bax and Caspase-3 in PC12 cells and in striatal neurons. Meanwhile, the EPO-dependent neuroprotection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/FoxO3a signalling pathway may be a possible mechanism involved in the neuroprotective effect of EPO in PD. PMID:24390959

  20. EPO-dependent activation of PI3K/Akt/FoxO3a signalling mediates neuroprotection in in vitro and in vivo models of Parkinson's disease.

    Science.gov (United States)

    Jia, Yu; Mo, Shi-Jing; Feng, Qi-Qi; Zhan, Ma-Li; OuYang, Li-Si; Chen, Jia-Chang; Ma, Yu-Xin; Wu, Jia-Jia; Lei, Wan-Long

    2014-05-01

    Erythropoietin (EPO) may become a potential therapeutic candidate for the treatment of the neurodegenerative disorder -- Parkinson's disease (PD), since EPO has been found to prevent neuron apoptosis through the activation of cell survival signalling. However, the underlying mechanisms of how EPO exerts its neuroprotective effect are not fully elucidated. Here we investigated the mechanism by which EPO suppressed 6-hydroxydopamine (6-OHDA)-induced neuron death in in vitro and in vivo models of PD. EPO knockdown conferred 6-OHDA-induced cytotoxicity. This effect was reversed by EPO administration. Treatment of PC12 cells with EPO greatly diminished the toxicity induced by 6-OHDA in a dose- and time-dependent manner. EPO effectively reduced apoptosis of striatal neurons and induced a significant improvement on the neurological function score in the rat models of PD. Furthermore, EPO increased the expression of phosphorylated Akt and phosphorylated FoxO3a, and abrogated the 6-OHDA-induced dysregulation of Bcl-2, Bax and Caspase-3 in PC12 cells and in striatal neurons. Meanwhile, the EPO-dependent neuroprotection was notably reversed by pretreatment with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). Our data suggest that PI3K/Akt/FoxO3a signalling pathway may be a possible mechanism involved in the neuroprotective effect of EPO in PD.

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

    Science.gov (United States)

    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

  2. Increased efficacy of the 6-hydroxydopamine lesion of the median forebrain bundle in small rats, by modification of the stereotaxic coordinates.

    Science.gov (United States)

    Torres, E M; Lane, E L; Heuer, A; Smith, G A; Murphy, E; Dunnett, S B

    2011-08-30

    The 6-hydroxydopamine (6-OHDA) lesion is the most widely used rat model of Parkinson's disease. A single unilateral injection of 6-OHDA into the median forebrain bundle (MFB) selectively destroys dopamine neurons in the ipsilateral substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), removing more than 95% of the dopamine innervation from target areas. The stereotaxic coordinates used to deliver 6-OHDA to the MFB have been used in our laboratory successfully for more than 25 years. However, in recent years we have observed a decline in the success rate of this lesion. Previously regular success rates of >80% of rats lesioned, have become progressively more variable, with rates as low as 20% recorded in some experiments. Having excluded variability of the neurotoxin and operator errors, we hypothesized that the change seen might be due to the use of smaller rats at the time of first surgery. An attempt to proportionally adjust the lesion coordinates base on head size did not increase lesion efficacy. However, in support of the small rat hypothesis it was observed that, using the standard coordinates, rat's heads had a "nose-up" position in the stereotaxic fame. Adjustment of the nose bar to obtain a flat head position during surgery improved lesion success, and subsequent adjustments of the lesion coordinates to account for smaller head size led to a greatly increased lesion efficacy (>90%) as assessed by amphetamine induced rotation.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  5. Dopaminergic differentiation of stem cells from human deciduous teeth and their therapeutic benefits for Parkinsonian rats.

    Science.gov (United States)

    Fujii, Hiromi; Matsubara, Kohki; Sakai, Kiyoshi; Ito, Mikako; Ohno, Kinji; Ueda, Minoru; Yamamoto, Akihito

    2015-07-10

    Parkinson's disease (PD) is a progressive neurodegenerative disorder caused by the loss of nigrostriatal dopaminergic (DAergic) neurons and the depletion of striatal dopamine. Here we show that DAergic-neuron-like cells could be efficiently induced from stem cells derived from human exfoliated deciduous teeth (SHEDs), and that these induced cells had therapeutic benefits in a 6-OHDA-induced Parkinsonian rat model. In our protocol, EGF and bFGF signaling activated the SHED's expression of proneural genes, Ngn2 and Mash1, and subsequent treatment with brain-derived neurotrophic factor (BDNF) promoted their maturation into DAergic neuron-like SHEDs (dSHEDs). A hypoxic DAergic differentiation protocol improved cell viability and enhanced the expression of multiple neurotrophic factors, including BDNF, GDNF, NT-3, and HGF. Engrafted dSHEDs survived in the striatum of Parkinsonian rats, improved the DA level more efficiently than engrafted undifferentiated SHEDs, and promoted the recovery from neurological deficits. Our findings further suggested that paracrine effects of dSHEDs contributed to neuroprotection against 6-OHDA-induced neurodegeneration and to nigrostriatal tract restoration. In addition, we found that the conditioned medium derived from dSHEDs protected primary neurons against 6-OHDA toxicity and accelerated neurite outgrowth in vitro. Thus, our data suggest that stem cells derived from dental pulp may have therapeutic benefits for PD.

  6. Electroacupuncture Alleviates Depressive-Like Symptoms and Modulates BDNF Signaling in 6-Hydroxydopamine Rats

    Science.gov (United States)

    Sun, Min; Wang, Ke; Yu, Yan; Su, Wen-Ting; Jiang, Xin-Xin

    2016-01-01

    Previous studies have identified the beneficial effects of electroacupuncture (EA) on motor behaviors in Parkinson's disease (PD). However, the role and potential mechanisms of EA in PD-associated depression remain unclear. In the present study, a rat model of PD with unilateral 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle was treated using EA for 4 weeks. We found that 100 Hz EA improved several motor phenotypes. In addition, tyrosine hydroxylase (TH) immunohistochemical analysis showed that EA had a minimal impact on the TH-positive profiles of the ipsilateral ventral tegmental area. Compared with the 6-OHDA group, long-term EA stimulation significantly increased sucrose solution consumption and decreased immobility time in the forced swim test. EA treatment did not alter dopamine, norepinephrine, and serotonin levels in the striatum and hippocampus. Noticeably, EA treatment reversed the 6-OHDA-induced abnormal expression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in the midbrain and hippocampus. These results demonstrate that EA at 100-Hz possesses the ability to improve depressive-like symptoms in PD rats, which is, at least in part, due to the distinct effect of EA on the mesostriatal and mesocorticolimbic dopaminergic pathways. Moreover, BDNF seems to participate in the effect of EA in PD. PMID:27525025

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

    DEFF Research Database (Denmark)

    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...

  8. The 6-hydroxydopamine-induced nigrostriatal neurodegeneration produces microglia-like NG2 glial cells in the rat substantia nigra.

    Science.gov (United States)

    Kitamura, Yoshihisa; Inden, Masatoshi; Minamino, Hideaki; Abe, Mari; Takata, Kazuyuki; Taniguchi, Takashi

    2010-11-01

    Neuron/glial 2 (NG2)-expressing cells are often referred to as oligodendrocyte precursor cells. NG2-expressing cells have also been identified as multipotent progenitor cells. However, microglia-like NG2 glial cells have not been fully examined in neurodegenerative disorders such as Parkinson's disease (PD). In the present study, we chose two rat models of PD, i.e., intranigral or intrastriatal injection of 6-hydroxydopamine (6-OHDA), since the cell bodies of dopamine (DA) neurons, which form a nigrostriatal pathway, are in the substantia nigra pars compacta (SNpc) while their nerve terminals are in the striatum. In the nigral 6-OHDA-injected model, activated NG2-positive cells were detected in the SNpc but not in the striatum. In contrast, in the striatal 6-OHDA-injected model, these cells were detected in both the SNpc and the striatum. In both models, activated NG2-positive cells were located close to surviving tyrosine hydroxylase (TH)-positive neurons in the SNpc. In addition, activated NG2-positive cells in the SNpc coexpressed ionized calcium-binding adaptor molecule 1 (Iba1), a microglia/macrophage marker. Interestingly, these double-positive glial cells coexpressed glial cell line-derived neurotrophic factor (GDNF). These results suggest that microglia-like NG2 glial cells may help protect DA neurons and may lead to new therapeutic targets in PD.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  14. Novel Food Supplement "CP1" Improves Motor Deficit, Cognitive Function, and Neurodegeneration in Animal Model of Parkinson's Disease.

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Sutalangka, Chatchada

    2016-08-01

    Based on pivotal roles of oxidative stress, dopaminergic and cholinergic systems on the pathophysiology of Parkinson's disease (PD), the searching for functional food for patients attacked with PD from Cyperus rotundus and Zingiber officinale, the substances possessing antioxidant activity, and the suppression effects on monoamine oxidase B (MAO-B) and acetylcholinesterase (AChE) have been considered. In this study, we aimed to determine the effect of the combined extract of C. rotundus and Z. officinale (CP1) to improve motor and memory deficits, neurodegeneration, oxidative stress, and functions of both cholinergic and dopaminergic systems in the animal model of PD induced by 6-hydroxydopamine hydrochloride (6-OHDA). Male Wistar rats, weighing 180-220 g, were induced unilateral lesion at right substantia nigra by 6-OHDA and were orally given CP1 at doses of 100, 200, and 300 mg/kg body weight for 14 days after 6-OHDA injection. The results showed that the 6-OHDA rats treated with CP1 increased spatial memory, but decreased neurodegeneration, malondialdehyde level, and AChE activity in hippocampus. The decreased motor disorder and neurodegeneration in substantia nigra together with the enhanced catalase activity, but decreased MAO-B activity in striatum, were also observed. The memory enhancing effect of CP1 might occur through the improved oxidative stress and the enhanced cholinergic function, whereas the effect to improve motor disorder of CP1 might occur through the enhanced dopaminergic function in striatum by decreasing the degeneration of dopaminergic neurons and the suppression of MAO-B. Therefore, CP1 is the potential functional food against PD. However, further researches in clinical trial and drug interactions are essential.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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;.

  2. 帕金森病大鼠模型的行为学及神经元形态学评价%Evaluation on behaviours and neuron morphology of Parkinson's disease rat model

    Institute of Scientific and Technical Information of China (English)

    陆建明; 周厚广

    2004-01-01

    背景:由于黑质致密部体积狭小,应用6-羟基多巴胺(6-Hydroxydopamine,6-OHDA)损毁黑质多巴胺神经元(Nigral dopaminergic neuron,NDN)制作帕金森病大鼠模型的成功率较低,一般仅为30%~40%左右.目的:探讨帕金森病大鼠模型建立后的行为学及神经元形态学改变.设计:完全随机的实验研究.地点和材料:安徽省药物研究所,SD大鼠,6-OHDA,阿朴吗啡,兔抗TH血清,SR-6N大鼠脑立体定向仪等.干预:将6-OHDA立体定向注射于90只SD大鼠的左侧黑质区及黑质纹状体通路,观察大鼠行为及多巴胺神经元形态学变化.主要观察指标:旋转行为,震颤及其他异常行为,免疫组织化学观察,电镜观察.结果:经阿朴吗啡诱导共筛选出64只成功大鼠模型(占71%);免疫组化观察发现注射侧黑质区NDN较对侧明显减少,电镜观察发现其普遍存在凋亡及坏死样改变.结论:本方法是建立帕金森病大鼠模型的有效方法,在行为学和神经元形态学等方面同帕金森病人有许多相似之处.%BACKGROUND: The successful rate in the establishment of Parkinson' s disease(PD) model in rat is comparatively low through destroying Nigral dopaminergic neuron (NDN) by 6-hydroxydopamine (6-OJDA) because of the small volume of pars compacta of substantia nigra(SNC), which is only about 30% to 40%.OBJECTIVE: To discuss the changes on behaviour and neuron morphology after the establishment of PD rat model.DESIGN: A complete random control study.SETTING and MATERIALS: Study was completed in the Pharmaceutical Institute of Anhui Province. Materials included SD rats, 6-OHDA, apomorphine,rabbit-anti-TH serum, SR-6N rat cerebral solid orientation apparatus, etc.INTERVENTIONS: 6-OHDA was solidly and directionally injected into left SN area and corpus striatum pathway in SN in 90 SD rats to observe the changes in the behaviours and dopaminergic neuron morphology.MAIN OUTCOME MEASURES: Rotation behaviour, tremor and other abnormal

  3. 脑内移植间充质干细胞治疗大鼠帕金森病模型的研究%Intracerebral Transplantation of Rat Bone Marrow-derived Mesenchymal Stem Cells for Treatment of 6-OHDA Model of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    付文玉; 邢海霞; 王晓萃; 吕娥; 王玉良; 郑志娟; 庄文欣

    2009-01-01

    目的 研究大鼠骨髓间充质干细胞(MSCs)脑内移植治疗帕金森病(PD)大鼠的可行性.方法 贴壁培养法分离、培养大鼠骨髓MSCs.将BrdU标记的第3代MSCs移植PD大鼠纹状体内,移植后1、2和4周检测PD大鼠的行为学变化,应用BrdU免疫荧光观察移植细胞在脑内的存活情况,应用免疫组化法检测酪氨酸羟化酶(TH)在移植细胞及黑质的表达.结果 移植细胞后1周、2周和4周PD大鼠与移植前相比行为学有改善,旋转圈数明显减少(P<0.05);PD大鼠损毁侧和健侧黑质内TH阳性细胞数之比随移植时间的延长而增加,但未发现移植细胞呈现TH阳性表达.细胞移植后1周、2周和4周检测均可见纹状体内BrdU阳性细胞散在分布.结论 植入脑内的MSCs能够生存和迁移,MSCs脑内移植对PD大鼠有一定的治疗作用.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  11. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

    2013-08-01

    Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease.

  12. Dietary and Intraperitoneal Administration of Selenium Provide Comparable Protection in the 6-Hydroxydopamine Lesion Rat Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Cecilia M. Fox

    2007-01-01

    Full Text Available Significant research implicates the involvement of free radicals in the manifestation of Parkinson's disease. The antioxidant, selenium is a vital dietary component for mammals. It is present in the active center of glutathione peroxidase, an antioxidant enzyme that scavenges peroxides and protects membrane lipids and macromolecules from oxidative insult. The purpose of this research was to determine an effective means of delivering selenium as well as an appropriate time frame for antioxidant administration that would elicit a protective response in rats challenged with an intranigral 6-hydroxydopamine (6-OHDA lesion. In the first part of this study, Fischer 344 rats were placed into one of four groups: selenium enhanced diet, control diet, intraperitoneal injection of selenium as Na2SeO3 or intraperitoneal injection of distilled water. All treatments were delivered prior to an intranigral 6-OHDA lesion. Animals were euthanized two weeks post lesion and their brains processed for tyrosine hydroxylase (TH immunocytochemistry. Average dopamine neuron survival in the substantia nigra of control animals was less than 22%; whereas nigral dopamine neuron survival in the selenium fed group was 49.7% and 56.0% in the selenium injected group. Based on these results, a subsequent study was designed utilizing the selenium enhanced diet method of antioxidant administration. To examine the neuroprotective effect of long-term selenium treatment, pregnant Fischer 344 rats were exposed to either selenium enhanced or control rat chow. Their pups were treated with the same diet as their mothers and lesioned with 6-OHDA at two months of age. Animals were euthanized and their brains were processed for TH immunocytochemistry. Nigral dopamine neuron survival for the selenium treated animals was significantly protective (59% when compared to the control chow fed animals (29.6%. However, when compared to the short-term exposure of selenium rat chow in the previous

  13. Efficient Expression of Igf-1 from Lentiviral Vectors Protects In Vitro but Does Not Mediate Behavioral Recovery of a Parkinsonian Lesion in Rats.

    Science.gov (United States)

    Lu-Nguyen, Ngoc B; Broadstock, Martin; Yáñez-Muñoz, Rafael J

    2015-11-01

    Gene therapy approaches delivering neurotrophic factors have offered promising results in both preclinical and clinical trials of Parkinson's disease (PD). However, failure of glial cell line-derived neurotrophic factor in phase 2 clinical trials has sparked a search for other trophic factors that may retain efficacy in the clinic. Direct protein injections of one such factor, insulin-like growth factor (IGF)-1, in a rodent model of PD has demonstrated impressive protection of dopaminergic neurons against 6-hydroxydopamine (6-OHDA) toxicity. However, protein infusion is associated with surgical risks, pump failure, and significant costs. We therefore used lentiviral vectors to deliver Igf-1, with a particular focus on the novel integration-deficient lentiviral vectors (IDLVs). A neuron-specific promoter, from the human synapsin 1 gene, excellent for gene expression from IDLVs, was additionally used to enhance Igf-1 expression. An investigation of neurotrophic effects on primary rat neuronal cultures demonstrated that neurons transduced with IDLV-Igf-1 vectors had complete protection on withdrawal of exogenous trophic support. Striatal transduction of such vectors into 6-OHDA-lesioned rats, however, provided neither protection of dopaminergic substantia nigra neurons nor improvement of animal behavior.

  14. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.

    Science.gov (United States)

    Danielyan, Lusine; Schäfer, Richard; von Ameln-Mayerhofer, Andreas; Bernhard, Felix; Verleysdonk, Stephan; Buadze, Marine; Lourhmati, Ali; Klopfer, Tim; Schaumann, Felix; Schmid, Barbara; Koehle, Christoph; Proksch, Barbara; Weissert, Robert; Reichardt, Holger M; van den Brandt, Jens; Buniatian, Gayane H; Schwab, Matthias; Gleiter, Christoph H; Frey, William H

    2011-02-01

    Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10⁶ MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine, 5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1 × 10⁶ cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their

  15. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    Science.gov (United States)

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

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

    Science.gov (United States)

    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

  17. Dopaminergic regeneration by neurturin-overexpressing c17.2 neural stem cells in a rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wang Gang

    2007-10-01

    Full Text Available Abstract Background Genetically engineered neural stem cell (NSC lines are promising vectors for the treatment of neurodegenerative diseases, particularly Parkinson's disease (PD. Neurturin (NTN, a member of the glial cell line-derived neurotrophic factor (GDNF family, has been demonstrated to act specifically on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for PD. In our previous work, we demonstrated that NTN-overexpressing c17.2 NSCs exerted dopaminergic neuroprotection in a rat model of PD. In this study, we transplanted NTN-c17.2 into the striatum of the 6-hydroxydopamine (6-OHDA PD model to further determine the regenerative effect of NTN-c17.2 on the rat models of PD. Results After intrastriatal grafting, NTN-c17.2 cells differentiated and gradually downregulated nestin expression, while the grafts stably overexpressed NTN. Further, an observation of rotational behavior and the contents of neurotransmitters tested by high-performance liquid chromatography showed that the regenerative effect of the NTN-c17.2 group was significantly better than that of the Mock-c17.2 group, and the regenerative effect of the Mock-c17.2 group was better than that of the PBS group. Further research through reverse-transcriptase polymerase chain reaction assays and in vivo histology revealed that the regenerative effect of Mock-c17.2 and NTN-c17.2 cell grafts may be attributed to the ability of NSCs to produce neurotrophic factors and differentiate into tyrosine hydroxylase-positive cells. Conclusion The transplantation of NTN-c17.2 can exert neuroregenerative effects in the rat model of PD, and the delivery of NTN by NSCs may constitute a very useful strategy in the treatment of PD.

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

    OpenAIRE

    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...

  19. Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats

    Directory of Open Access Journals (Sweden)

    Ito Mikako

    2012-05-01

    Full Text Available Abstract Background Lactulose is a synthetic disaccharide that can be catalyzed only by intestinal bacteria in humans and rodents, and a large amount of hydrogen is produced by bacterial catalysis of lactulose. We previously reported marked effects of ad libitum administration of hydrogen water on prevention of a rat model of Parkinson’s disease (PD. Methods End-alveolar breath hydrogen concentrations were measured in 28 healthy subjects and 37 PD patients, as well as in 9 rats after taking hydrogen water or lactulose. Six-hydroxydopamine (6-OHDA-induced hemi-PD model was stereotactically generated in rats. We compared effects of hydrogen water and lactulose on prevention of PD. We also analyzed effects of continuous and intermittent administration of 2% hydrogen gas. Results Hydrogen water increased breath hydrogen concentrations from 8.6 ± 2.1 to 32.6 ± 3.3 ppm (mean and SEM, n = 8 in 10 min in healthy subjects. Lactulose increased breath hydrogen concentrations in 86% of healthy subjects and 59% of PD patients. Compared to monophasic hydrogen increases in 71% of healthy subjects, 32% and 41% of PD patients showed biphasic and no increases, respectively. Lactulose also increased breath hydrogen levels monophasically in 9 rats. Lactulose, however, marginally ameliorated 6-OHDA-induced PD in rats. Continuous administration of 2% hydrogen gas similarly had marginal effects. On the other hand, intermittent administration of 2% hydrogen gas prevented PD in 4 of 6 rats. Conclusions Lack of dose responses of hydrogen and the presence of favorable effects with hydrogen water and intermittent hydrogen gas suggest that signal modulating activities of hydrogen are likely to be instrumental in exerting a protective effect against PD.

  20. 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

    Directory of Open Access Journals (Sweden)

    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.

  1. The Involvement of Akt Activation in Erythropoietin Induced Neuroprotection in Rat Model of Parkinson’s Disease%丝氨酸/苏氨酸激酶通路参与促红细胞生成素保护帕金森病大鼠的实验研究

    Institute of Scientific and Technical Information of China (English)

    戚辰; 干静; 吴娜; 宋璐; 袁伟恩; 刘振国

    2014-01-01

    目的:观察促红细胞生成素(EPO)对帕金森病(PD)模型大鼠的保护作用并探讨其机制。方法实验大鼠分为3组,①PD组:6-羟基多巴(6-OHDA)定向注射至右侧前脑内侧束建立PD模型;②EPO组:在模型制备前持续1周给予腹腔注射EPO10000U·kg-1·d-1;③假手术组:大鼠脑内立体定向注射生理盐水。采用ELISA法检测大鼠脑脊液EPO含量变化,术后3周评估大鼠行为学改变,免疫组化学、免疫荧光及蛋白印迹法分别检测酪氨酸羟化酶(TH)、EPO受体(EPO-R)及丝氨酸/苏氨酸激酶(Akt)磷酸化(Ser473)的表达。结果①EPO组脑脊液内EPO含量[(416.59±9.34)µU·L-1]增加,与假手术组[(2.20±1.92)µU·L-1]比较,差异有统计学意义(P﹤0.05);②EPO组的行为学改善,黑质多巴胺能神经元的丢失减少,黑质EPO-R的表达增加,与PD组及假手术组比较,差异有统计学意义(P﹤0.05);③EPO组黑质Akt磷酸化(Ser473)的表达明显增加,与PD组及假手术组比较,差异有统计学意义(P﹤0.05)。结论 EPO腹腔注射可以改善PD大鼠的运动症状,与EPO增加PD大鼠的磷酸化Akt(Ser473)表达可能有关。%Aim To investigate the neuroprotection of erythropoietin in a rat model of Parkinson’s disease (PD) and explore the mechanisms underlying these effects. Methods The rats were divided into three groups. The rats model of PD were induced by stereotactic injection of 6-OHDA.EPO (10 000 U·kg-1·d-1) was continuously administered intraperitoneal injection for a week to the rats before 6-OHDA injection. The sham operation group stereotactic injected of saline. Neurobehavior in rats were measured in 3 weeks after the treatments.Survival of substantia nigra (SN) dopaminergic neurons, tyrosine hydroxylase (TH) levels and EPO-R levels and phosphoprotein of serine-threonine kinase(Akt) at serine 473 levels were determined by immunohistochemistry and Western blot respectively. Results There was

  2. [18F]desmethoxyfallypride as a novel PET radiotracer for quantitative in vivo dopamine D2/D3 receptor imaging in rat models of neurodegenerative diseases

    International Nuclear Information System (INIS)

    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.

  3. Alterations of BDNF and trkB mRNA expression in the 6-hydroxydopamine-induced model of preclinical stages of Parkinson's disease: an influence of chronic pramipexole in rats.

    Directory of Open Access Journals (Sweden)

    Klemencja Berghauzen-Maciejewska

    Full Text Available Our recent study has indicated that a moderate lesion of the mesostriatal and mesolimbic pathways in rats, modelling preclinical stages of Parkinson's disease, induces a depressive-like behaviour which is reversed by chronic treatment with pramipexole. The purpose of the present study was to examine the role of brain derived neurotrophic factor (BDNF signalling in the aforementioned model of depression. Therefore, we investigated the influence of 6-hydoxydopamine (6-OHDA administration into the ventral region of the caudate-putamen on mRNA levels of BDNF and tropomyosin-related kinase B (trkB receptor. The BDNF and trkB mRNA levels were determined in the nigrostriatal and limbic structures by in situ hybridization 2 weeks after the operation. Pramipexole (1 mg/kg sc twice a day and imipramine (10 mg/kg ip once a day were injected for 2 weeks. The lesion lowered the BDNF and trkB mRNA levels in the hippocampus [CA1, CA3 and dentate gyrus (DG] and amygdala (basolateral/lateral as well as the BDNF mRNA content in the habenula (medial/lateral. The lesion did not influence BDNF and trkB expression in the caudate-putamen, substantia nigra, nucleus accumbens (shell and core and ventral tegmental area (VTA. Chronic imipramine reversed the lesion-induced decreases in BDNF mRNA in the DG. Chronic pramipexole increased BDNF mRNA, but decreased trkB mRNA in the VTA in lesioned rats. Furthermore, it reduced BDNF and trkB mRNA expression in the shell and core of the nucleus accumbens, BDNF mRNA in the amygdala and trkB mRNA in the caudate-putamen in these animals. The present study indicates that both the 6-OHDA-induced dopaminergic lesion and chronic pramipexole influence BDNF signalling in limbic structures, which may be related to their pro-depressive and antidepressant activity in rats, respectively.

  4. Iptakalim hydrochloride protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models.

    Science.gov (United States)

    Yang, Yan-Ling; Meng, Chang-Hong; Ding, Jian-Hua; He, Hai-Rong; Ellsworth, Kevin; Wu, Jie; Hu, Gang

    2005-07-01

    Iptakalim hydrochloride (Ipt), a novel antihypertensive drug, exhibits K(ATP) channel activation. Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. Chronic exposure of cultured PC12 cells to neurotoxins, such as 6-OHDA, MPP+, or rotenone, decreased overall [3H]-glutamate uptake in a concentration-dependent manner. Pre-treatment using 10 microM Ipt significantly protected cells against neurotoxin-induced glutamate uptake diminishment, and this protection was abolished by the K(ATP) channel blocker glibenclamide (20 microM), suggesting that the protective mechanisms may involve the opening of K(ATP) channels. In 6-OHDA-treated rats (as an in vivo Parkinson's disease model), [3H]-glutamate uptake was significantly lower in synaptosomes isolated from the striatum and cerebral cortex, but not the hippocampus. Pre-conditioning using 10, 50, and 100 microM Ipt significantly restored glutamate uptake impairment and these protections were abolished by blockade of K(ATP) channels. It is concluded that Ipt exhibits substantial protection of cells against neurotoxicity in in vitro and in vivo models. The cellular mechanisms of this protective effect may involve the opening of K(ATP) channels. Collectively, Ipt may serve as a novel and effective drug for PD therapy.

  5. Rat Endovascular Perforation Model

    OpenAIRE

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Deng, Xingli; Liang, Yuanxin; Lu, Hua; Yang, Zhiyong; Liu, Ru'en; Wang, Jinkun; Song, Xiaobin; Long, Jiang; Li, Yu; Lei, Deqiang; Feng, Zhongtang

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  15. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Anterior ventral tegmental area dopaminergic neurons are not involved in the motivational effects of bromocriptine, pramipexole and cocaine in drug-free rats.

    Science.gov (United States)

    Ouachikh, Omar; Dieb, Wisam; Durif, Franck; Hafidi, Aziz

    2014-04-01

    Dopamine dysregulation syndrome in Parkinson's disease has been attributed to dopamine replacement therapies and/or a lesion of the dopaminergic system. Dopaminergic neuronal loss targets the substantia nigra and the ventral tegmental area (VTA). We hypothesize that dopamine replacement therapy is responsible for the potential reinforcement effect in Parkinson's disease, by acting on the neuronal reward circuitry. We previously demonstrated that the posterior (p) VTA, which projects to the nucleus accumbens (NAc), is implicated in the motivational effect of dopamine receptor agonists in 6-OHDA bilateral pVTA-lesioned drug-free animals. In the present study we investigated the implication of the anterior (a) VTA in the potential reinforcement effect of dopamine receptor agonists. Using the conditioned place preference (CPP) behavioral paradigm, we investigated the motivational effects of dopamine receptor agonists (bromocriptine and pramipexole), and cocaine in rats with a 6-OHDA bilateral lesion of the aVTA. Bromocriptine and pramipexole did not induce a significant CPP at 1mg/kg in both sham and bilateral 6-OHDA-lesioned rats. However bromocriptine induced CPP only at a dose of 3mg/kg in both animal groups. Moreover cocaine, which is known to increase dopamine release, induced reinforcing effects in both 6-OHDA-lesioned and sham rats. Our data show a lack of involvement of aVTA dopamine neurons in the motivational effects of bromocriptine, pramipexole and cocaine.

  17. 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

    Institute of Scientific and Technical Information of China (English)

    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

  18. The effects of prenatal methylmercury exposure on trace element and antioxidant levels in rats following 6-hydroxydopamine-induced neuronal insult.

    Science.gov (United States)

    Mohamed Moosa, Zulfiah; Daniels, Willie M U; Mabandla, Musa V

    2014-06-01

    Methylmercury (MeHg) is a metal toxin found commonly in the environment. Studies have shown severe neurotoxic effects of MeHg poisoning especially during pregnancy where it crosses the foetoplacental and the blood brain barrier of the foetus leading to neurodevelopmental deficits in the offspring. These deficits may predispose offspring to neurodegenerative diseases later in life. In this study we investigated the effects of prenatal methylmercury exposure (2.5 mg/L in drinking water from GND 1-GND 21) on the trace element status in the brain of adolescent offspring (PND 28). Total antioxidant capacity (TAC) was measured in their blood plasma. In a separate group of animals that was also exposed prenatally to MeHg, 6-hydroydopamine (6-OHDA) was administered at PND 60 as a model of neuronal insult. Trace element and TAC levels were compared before and after 6-OHDA exposure. Prenatal MeHg treatment alone resulted in significantly higher concentrations of zinc, copper, manganese and selenium in the brain of offspring at PND 28 (p levels in MeHg-exposed adolescent offspring were significantly lower than their controls (p levels of iron, zinc, copper and manganese were increased compared to sham-lesioned offspring (p levels thereby promoting toxicity (p levels were higher in adult male rats than in female rats during adolescence however male rats that had been exposed to MeHg in utero failed to show this increase at PND 74. Prenatal MeHg exposure results in trace element dyshomeostasis in the brain of offspring and reduces total antioxidant capacity. This may reflect a mechanism by which methylmercury exerts its neurotoxicity and/or predispose offspring to further neurological insults during adulthood.

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Reynosin protects against neuronal toxicity in dopamine-induced SH-SY5Y cells and 6-hydroxydopamine-lesioned rats as models of Parkinson's disease: Reciprocal up-regulation of E6-AP and down-regulation of α-synuclein.

    Science.gov (United States)

    Ham, Ahrom; Kim, Dong-Woo; Kim, Kyeong Ho; Lee, Sung-Jin; Oh, Ki-Bong; Shin, Jongheon; Mar, Woongchon

    2013-08-01

    Aggregation of α-synuclein (ASYN) is considered a major determinant of neuronal loss in Parkinson's disease (PD). E6-associated protein (E6-AP), an E3 ubiquitin protein ligase, has been known to promote the degradation of α-synuclein. The aim of this study was to assess the effects of the sesquiterpene lactone reynosin on dopamine (DA)-induced neuronal toxicity and regulation of E6-associated protein and α-synuclein proteins in both in vitro and in vivo models of Parkinson's disease. Usi"ng flow cytometry and western blot analysis, we determined that reynosin significantly protected both against cell death from dopamine-induced toxicity in human neuroblastoma SH-SY5Y cells and against the loss of tyrosine hydroxylase (TH)-positive cells in 6-hydroxydopamine (6-OHDA)-lesioned rats (a rodent Parkinson's disease model system). In addition, reynosin made up-regulation of E6-associated protein expression and down-regulation of the over-expression of α-synuclein protein in both dopamine-treated SH-SY5Y cells and 6-hydroxydopamine-lesioned rats. These results suggest that the protective effect of reynosin against dopamine-induced neuronal cell death may be due to the reciprocal up-regulation of E6-associated protein and down-regulation of α-synuclein protein expression.

  2. Comparative study of the neurotrophic effects elicited by VEGF-B and GDNF in preclinical in vivo models of Parkinson's disease.

    Science.gov (United States)

    Yue, X; Hariri, D J; Caballero, B; Zhang, S; Bartlett, M J; Kaut, O; Mount, D W; Wüllner, U; Sherman, S J; Falk, T

    2014-01-31

    Vascular endothelial growth factor B (VEGF-B) has recently been shown to be a promising novel neuroprotective agent for several neurodegenerative conditions. In the current study we extended previous work on neuroprotective potential for Parkinson's disease (PD) by testing an expanded dose range of VEGF-B (1 and 10 μg) and directly comparing both neuroprotective and neurorestorative effects of VEGF-B in progressive unilateral 6-hydroxydopamine (6-OHDA) PD models to a single dose of glial cell line-derived neurotrophic factor (GDNF, 10 μg), that has been established by several groups as a standard in both preclinical PD models. In the amphetamine-induced rotational tests the treatment with 1 and 10 μg VEGF-B resulted in significantly improved motor function of 6-OHDA-lesioned rats compared to vehicle-treated 6-OHDA-lesioned rats in the neuroprotection paradigm. Both doses of VEGF-B caused an increase in tyrosine hydroxylase (TH)-positive cell and fiber count in the substantia nigra (SN) and striatum in the neuroprotective experiment. The effect size was comparable to the effects seen with GDNF. In the neurorestoration paradigm, VEGF-B injection had no significant effect in either the behavioral or the immunohistochemical analyses, whereas GDNF injection significantly improved the amphetamine-induced rotational behavior and reduced TH-positive neuronal cell loss in the SN. We also present a strong positive correlation (p=1.9e-50) of the expression of VEGF-B with nuclear-encoded mitochondrial genes involved in fatty acid metabolism in rat midbrain, pointing to the mitochondria as a site of action of VEGF-B. GDNF showed a positive correlation with nuclear-encoded mitochondrial genes that was not nearly as strong (p=0.018). VEGF-B counteracted rotenone-induced reduction of (a) fatty acid transport protein 1 and 4 levels and (b) both Akt protein and phosphorylation levels in SH-SY5Y cells. We further verified VEGF-B expression in the human SN pars compacta of healthy

  3. Nogo-A Neutralization Improves Graft Function in a Rat Model of Parkinson’s Disease

    Science.gov (United States)

    Seiler, Stefanie; Di Santo, Stefano; Widmer, Hans Rudolf

    2016-01-01

    Transplantation of fetal human ventral mesencephalic (VM) dopaminergic neurons into the striatum is a promising strategy to compensate for the characteristic dopamine deficit observed in Parkinson’s disease (PD). This therapeutic approach, however, is currently limited by the high number of fetuses needed for transplantation and the poor survival and functional integration of grafted dopaminergic neurons into the host brain. Accumulating evidence indicates that contrasting inhibitory signals endowed in the central nervous system (CNS) might support neuronal regeneration. Hence, in the present study we aimed at improving survival and integration of grafted cells in the host brain by neutralizing Nogo-A, one of the most potent neurite growth inhibitors in the CNS. For that purpose, VM tissue cultures were transplanted into rats with a partial 6-hydroxydopamine (6-OHDA) lesion causing a hemi-PD model and concomitantly treated for 2 weeks with intra-ventricular infusion of neutralizing anti-Nogo-A antibodies. Motor behavior using the cylinder test was assessed prior to and after transplantation as functional outcome. At the end of the experimental period the number of dopaminergic fibers growing into the host brain, the number of surviving dopaminergic neurons in the grafts as well as graft size was examined. We found that anti-Nogo-A antibody infusion significantly improved the asymmetrical forelimb use observed after lesions as compared to controls. Importantly, a significantly three-fold higher dopaminergic fiber outgrowth from the transplants was detected in the Nogo-A antibody treated group as compared to controls. Furthermore, Nogo-A neutralization showed a tendency for increased survival of dopaminergic neurons (by two-fold) in the grafts. No significant differences were observed for graft volume and the number of dopaminergic neurons co-expressing G-protein-coupled inward rectifier potassium channel subunit two between groups. In sum, our findings support the

  4. Nogo-A Neutralization Improves Graft Function in a Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Seiler, Stefanie; Di Santo, Stefano; Widmer, Hans Rudolf

    2016-01-01

    Transplantation of fetal human ventral mesencephalic (VM) dopaminergic neurons into the striatum is a promising strategy to compensate for the characteristic dopamine deficit observed in Parkinson's disease (PD). This therapeutic approach, however, is currently limited by the high number of fetuses needed for transplantation and the poor survival and functional integration of grafted dopaminergic neurons into the host brain. Accumulating evidence indicates that contrasting inhibitory signals endowed in the central nervous system (CNS) might support neuronal regeneration. Hence, in the present study we aimed at improving survival and integration of grafted cells in the host brain by neutralizing Nogo-A, one of the most potent neurite growth inhibitors in the CNS. For that purpose, VM tissue cultures were transplanted into rats with a partial 6-hydroxydopamine (6-OHDA) lesion causing a hemi-PD model and concomitantly treated for 2 weeks with intra-ventricular infusion of neutralizing anti-Nogo-A antibodies. Motor behavior using the cylinder test was assessed prior to and after transplantation as functional outcome. At the end of the experimental period the number of dopaminergic fibers growing into the host brain, the number of surviving dopaminergic neurons in the grafts as well as graft size was examined. We found that anti-Nogo-A antibody infusion significantly improved the asymmetrical forelimb use observed after lesions as compared to controls. Importantly, a significantly three-fold higher dopaminergic fiber outgrowth from the transplants was detected in the Nogo-A antibody treated group as compared to controls. Furthermore, Nogo-A neutralization showed a tendency for increased survival of dopaminergic neurons (by two-fold) in the grafts. No significant differences were observed for graft volume and the number of dopaminergic neurons co-expressing G-protein-coupled inward rectifier potassium channel subunit two between groups. In sum, our findings support the

  5. Animal models to guide clinical drug development in ADHD: lost in translation?

    Science.gov (United States)

    Wickens, Jeffery R; Hyland, Brian I; Tripp, Gail

    2011-10-01

    We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open-field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6-hydroxydopamine-lesioned (6-OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6-OHDA-lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    OpenAIRE

    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...

  12. Changes and roles of endogenous hydrogen sulfide in the substantial nigra oxidative damage of rats%内源性硫化氢在大鼠黑质氧化损伤中的变化及作用

    Institute of Scientific and Technical Information of China (English)

    许岩; 马娜; 刘博; 王晶莹; 廖文辉; 汪胜; 王金全; 孟金兰

    2014-01-01

    Objective To observe the changes and roles of endogenous hydrogen sulfide in the substantia nigra oxida-tive damage of rats. Methods 6-hydroxydop- amine (6-OHDA) was microinjected in the unilateral substantia nigra of SD rats as the substantia nigra oxidative damage model;H2S donor, sodium hydrosulfide (NaHS) was injected intraperi-toneally for three consecutive weeks as a pretreatment before 6-OHDA injury. The experiment were divided into the control group , 7 days (D7) group, 11 days (D11) group, 17 days (D17) group after 6-OHDA injury and NaHS precondi-tioning group (deafed with NaHS + 6-OHDA); with 8 rats in each group. Cystathionine-β-synthase (CBS) activity and H2S production in substantia nigra were detected by methylene blue spectrophot-ometric method. Immunohistochemistry was used to detect tyrosine hydroxylase (tyrosine hydroxylase, TH) positive cells of the substantia nigra; Glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) level of the substantia nigra were measured by UV spec-trophotometry. Results Compared with the control group, percentage of CBS activity was decreased re-spectively to [(96.21±8.40)%, P > 0.05], [(86.48±9.85)%, P0.05],[(86.48±9.85)%,P<0.05]和[(75.16±7.45)%,P<0.01];内源性H2S含量分别减少为[(90.12±10.03)%,P<0.05],[(82.58±9.52)%,P<0.01]和[(78.16±11.55)%,P<0.01]。 TH阳性细胞与对照组比较,在6-OHDA损伤后7 d即下降为[(84.32±6.06)%,P<0.05],同时伴随黑质GSH-Px活性降低及MDA含量升高,差异有统计学意义(P<0.05)。但早期给予NaHS预处理补充H2S之后,与单纯6-OHDA损伤后7 d比较,TH阳性细胞则增加为[(96.15±5.03)%,P<0.05],且黑质GSH-Px的活性升高,MDA的含量降低,差异有统计学意义(P<0.05)。结论6-OHDA氧化损伤导致大鼠黑质CBS酶活性及H2S含量下降,外源性H2S预处理可早期发挥抗黑质氧化损伤的神经元保护作用,这可能与其增加GSH-Px活性及减少MDA含量有关。

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  15. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  18. Modeling nicotine addiction in rats.

    Science.gov (United States)

    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

  19. Protective effects of H2S on dopamine neurons in rats with Parkinson's disease%硫化氢对帕金森病模型大鼠多巴胺神经元的保护作用

    Institute of Scientific and Technical Information of China (English)

    尹蔚兰; 何剑琴; 张恺芳; 欧阳新平

    2011-01-01

    目的:观察硫化氢对帕金森病(Parkinson's disease,PD)大鼠神经行为学、氧化应激以及多巴胺及其代谢产物的影响.方法:采用6-羟基多巴胺(6-OHDA)注射于脑右侧黑质造成偏侧PD模型.将模型动物随机分为模型组、硫化氢组(硫氢化钠做供体),每组10只;另分别取10只正常大鼠为正常组及假手术组(以抗坏血酸注射).观察PD大鼠经过硫化氢处理后神经行为学、脑组织丙二醛(MDA)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)含量以及多巴胺代谢产物的变化.结果:与模型组比较硫化氧组大鼠行为学明显改善(P<0.01),同时脑组织中GSH、SOD含量均升高,MDA含量降低,多巴胺及其代谢产物升高.结论:硫化氢对PD模型大鼠多巴胺神经元具有保护作用.%Objective: To observe the effects of H2S prescription on neuroethology, oxidative stress, dopamine and its metabolites in rats with Parkinson's disease (PD).Methods: Model of hemilateral PD mt was established with injection of 6-hydroxydopamine( 6-OHDA )into the right substantia nigra of midbrain.The PD model rats were randomly divided into model group, H2S group (sodium hydrosulfide, NariS, was used as H2S donor), control group and sham-operated group( injected by ascorbic acid) ,10 rats for each group.The changes of neuroethology, the contents of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and the levels of dopamine and its metabolites were compared among groups.Results: Compared with model group, the neuroethology of rats in H2S group were significantly improved.The contents of GSH, SOD were reduced significanfiy; The contents of MDA and the levels of dopamine( DA ),HVA, dihydroxv-phenyl acetic acid (DOPAC) were elevated significantly.Conclusion: H2S can protect the dopamine neurons in rats with Parkinson's disease.

  20. Rat model for human cryptosporidiosis.

    OpenAIRE

    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 ...

  1. 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

    OpenAIRE

    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...

  2. The effects of constraint-induced movement therapy on expression of tyrosine hydroxylase and glial cell derived neurotrophic factor in Parkinson's disease model rats%强制性运动训练对帕金森病大鼠酪氨酸羟化酶及胶质细胞源性神经营养因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    黄月; 张善锋; 任秀花; 张杰文

    2012-01-01

    Objective To explore the effects of constraint-induced movement therapy (CIMT) on the expression of tyrosine hydroxylase (TH) and glial cell derived neurotrophic factor (GDNF) in Parkinson's disease (PD) model rats. Methods PD models were established by microinjection of 6-hydroxydopamine (6-OHDA) solution into substantia nigra of rats' right cerebral hemisphere.Forty-two model rats were divided randomly into an exercise group and a control group 1 week after microinjection.The exercise group rats were forced to use their impaired limbs by placing their nonimpaired fore-limbs in casts.The control group rats were housed in the same environment without any special treatment.Two weeks after 6-OHDA infusion and exercise training,the behavioral changes of rats were examined after intraperitoneal injection apomorphine ( APO).The content of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) was measured by high performance liquid chromatography with electrochemistry ( HPLAEC) ; the expressions of TH and GDNF in striatum were detected by immunohistochemical methods and TH,GDNF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Results After 2 weeks of training,the rotating laps of the rats in exercise group within 30 min after APO induction,reduced to a significantly greater extent when compared to the control group (P < 0.05).The content of DA and it's metabolites DOPAC in striatum homogenate was significantly higher in exercise group than that in the control group ( P < 0.05 ),and the expression levels,of TH and GDNF protein/ mRNA were also significantly higher in the exercise group than those in control group ( P < 0.05 ). Conclusions CIMT can improve the behavioral performance of PD rats,probably through promoting the expressions of TH and GDNF protein/mRNA in striatum,and increasing DA and it's metabolites DOPAC level.%目的 观察强制性运动训练对帕金森病(PD)模型大鼠酪氨酸羟化酶(TH)及胶质细胞源性神

  3. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  4. Effect of electroacupuncture on Nestin, PCNA and Tuj1 expression in neural stem cells of substantia nigra in the Parkinson's disease model rats%电针对帕金森病模型大鼠黑质神经干细胞巢蛋白、PCNA和β-微管蛋白表达的作用

    Institute of Scientific and Technical Information of China (English)

    倪进忠; 丁艳霞; 熊克仁

    2012-01-01

    目的:研究不同频率和疗程电针对帕金森病(PD)模型大鼠黑质致密部(SNc)神经干细胞(NSC)表达的影响.方法:SD大鼠随机分为16组,正常对照组,1、2、3周假手术组、模型组、1、2、3疗程美多巴组、低频电针组、高频电针组,采用右侧纹状体内注射6-羟基多巴胺(6-OHDA)制备PD模型,取合谷和太冲穴,分别给予低频(2 Hz)和高频(100 Hz)电针治疗.免疫组织化学观察黑质致密部的巢蛋白、PCNA和β-微管蛋白(Tuj1)表达.结果:PD模型大鼠黑质致密部的巢蛋白、PCNA和Tuj1表达增加,高频电针可增加其巢蛋白、PCNA和Tuj1表达,低频电针对其没有影响.结论:高频电针可增加黑质致密部自体NSC的增殖,并诱导其向神经元前体细胞分化.%Objective; To explore the expression changes of proteins related neural stem cells (NSC) in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) model rats treated with different frequency and course of electroacupuncture (EA). Methods; Ninty-six Sprague-Dawley rats were randomly divided into sixteen groups:a normal control group; 1-. 2- and 3- week sham-operated groups, a model group; 1-, 2- and 3- course of Madopar treatment groups, a low-frequency EA treatment group, and a high-frequency EA treatment group. The PD model was prepared by injection of 6-hydroxydo-pamine (6-OHDA) into the right striatum. "Hegu" and "Taichong" were given low-frequency (2 Hz) and high-frequency (100 Hz) EA treatment Immunohistochemistry was used to observe the Nestin, proliferating cell nuclear antigen (PCNA) and β-tubulin isotype-Ⅲ (Tujl) expression in SNc. Results-. The expression of Nestin, PCNA, Tujl increased in SNc of the PD model rats. The high-frequency EA improved its Nestin, PCNA and Tujl expression, while the low-frequency EA had no effect. Conclusion-. High-frequency EA can improve the autologous NSC proliferation of SNc and induce the differentiation into neuronal precursor cells.

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

    OpenAIRE

    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...

  6. Penile autotransplantation in rats: An animal model

    Directory of Open Access Journals (Sweden)

    Raouf M Seyam

    2013-01-01

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

  7. Penile autotransplantation in rats: An animal model

    OpenAIRE

    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...

  8. Influence on behavior of rats with Parkinson's disease treated by bone mesenchymal stem cell modified by plasmid pIRESneo-EGFP-BDNF%转染pIRESneo-EGFP-BDNF的骨髓间充质干细胞侧脑室注射对帕金森大鼠行为学的影响

    Institute of Scientific and Technical Information of China (English)

    张平; 赵钢勇; 宋月平; 苏立凯

    2012-01-01

    [目的]观察转染pIRESneo- EGFP-BDNF的骨髓间充质干细胞(MSCs)侧脑室注射对帕金森病(PD)大鼠行为学的影响.[方法]将pEGFP(N1)-BDNF与pIRESneo进行双酶切后再连接,构建高拷贝质粒pIRESneo-EGFPBDNF,采用电穿孔法将其转染MSCs.采用6-羟多巴(6-OHDA)制备PD大鼠模型(36只),造模成功后将其随机分为3组,每组12只.B组为模型组:侧脑室注射生理盐水;C组:侧脑室注射MSCs;D组:侧脑室注射转染pIRESneoEGFP-BDNF的MSCs;A组(12只大鼠,为假手术组):以生理盐水代替6-OHDA后,侧脑室注射生理盐水.分别于侧脑室注射后2、4、8周腹腔注射阿扑吗啡(APO)诱导大鼠旋转,观察各组大鼠行为学变化.[结果]经双酶切鉴定,pIRESneo-EGFP-BDNF构建成功.侧脑室注射细胞干预PD大鼠模型后2、4、8周,大鼠旋转次数D组<C组<B组(P均<0.05);D组大鼠旋转次数明显减少,但仍较A组多.[结论]侧脑室注射转染plRESneo-EGFP-BDNF的MSCs能明显改善PD大鼠的行为能力.%Objective To observe influence on behavior of Parkinson's disease( PD) model treated by bone mesen-chymal stem cells ( MSCs) modified by plasmid pIRESneo-EGFP-BDNF. Methods pEGFP-BDNF and pIRESneo were double enzymed and then were reconstructed into pIRESneo-EGFP-BDNF which was transfected to MSCs with electroproa-lion. 36 rat models of PD were set up by 6-OHDA and divided into three groups randomly; group B( group model): inlrac-erebrovenlricular injection of saline; group C: intracerebroventricular injection of bone MSCs; group D: intracerebroventric-ular injection of bone MSCs modefied by pIRESneo-ECFP-BDNF. Group A (12 rats, sham opreation groups): saline instead of 6-OHDA, than intracerebroventricular injection of saline. The rotating behavior of rat models induced by Apomor-phine intraperitoneally which transplanting bone MSCs or MSCs modified by plasmid pIRESneo-EGFP-BDNF through cerebral lateral ventricle after 2, 4 and 8 weeks. Results Pbsmids p

  9. Behavioral effects of lesions in the A10 dopaminergic area of the rat.

    Science.gov (United States)

    Galey, D; Simon, H; Le Moal, M

    1977-03-18

    Experiments have been carried out with 150 rats in order to study some psychophysiological functions of the mesencephalocortico limbic dopaminergic A10 group. Lesions in the A10 area were made by using 6-hydroxydopamine (6-OHDA) local injections; 2 small volumes of injections were used at the same concentration (2 mug/1 mul or 1 mug/0.5 mul). In a first experiment the effects of these two injections were tested on locomotor activity measured in a circular corridor, 10 and 30 days after surgery. Injections provoked hyperactivity, mainly during nocturnal basal activity periods, but not during initial exploratory activity periods. The larger the injection, the more important the hyperactivity was. The larger injections induced important food spillage evidence through the wire floor of the home cage and perturbation in a passive avoidance learning. There was no change in body weight or in amount of ingested food. In a second experiment, the effects of local injection of 6-OHDA in the other CA structures or bundles situated in or near the ventral tegmental area were tested. Injections in the substantia nigra compacta, in the noradrenergic ventral bundle, in the dorsal periventricular system-tegmental radiations did not provoke locomotor hyperactivity. In a third experiment, a possible role of the median raphe (MR) nucleus in the A10-lesion induced hyperactivity was tested: first, radiofrequency MR lesions were made and no durable significant hyperactivity was recorded; secondly, 6-OHDA (1 mug/0.5 mul) was injected into the A10 area and activity was measured 10 days later: these injections provoked significant hyperactivity during the nocturnal basal and the diurnal basal activity periods. It might be concluded that neither the neighboring CA fibers nor the MR were directly involved in the ventral tegmental -- 6-OHDA lesions syndrome. Anatomical controls by using the Fink-Heimer silver impregnating method have demonstrated, first, that the 6-OHDA injections did not

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat

    DEFF Research Database (Denmark)

    Meyer, Morten; Widmer, H R; Wagner, B;

    1998-01-01

    . The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival...... improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

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

    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...

  15. Dietary models for inducing hypercholesterolemia in rats

    OpenAIRE

    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...

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. A rat model for hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Yannick Debing

    2016-10-01

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

  18. A rat model for hepatitis E virus

    Science.gov (United States)

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Experimental rat bladder urothelial cell carcinoma models

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

    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....

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

    Directory of Open Access Journals (Sweden)

    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.

  5. A model of subarachnoid hemorrhage in rats

    Institute of Scientific and Technical Information of China (English)

    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

  6. Rat Model of Parkes Weber Syndrome.

    Directory of Open Access Journals (Sweden)

    Krzysztof Bojakowski

    Full Text Available The Parkes Weber syndrome is a congenital vascular malformation, characterized by varicose veins, arterio-venous fistulas and overgrown limbs. No broadly accepted animal model of Parkes Weber syndrome has been described. We created side-to-side arterio-venous fistula between common femoral vessels with proximal non-absorbable ligature on common femoral vein limiting the enlargement of the vein diameter in Wistar rats. Contralateral limb was sham operated. Invasive blood pressure measurements in both iliac and inferior cava veins were performed in rats 30 days after fistula creation. Tight circumference and femoral bone length were measured. Histopathology and morphology of soleus muscle, extensor digitorum longus muscle, and the common femoral vessel were analyzed. 30 days following arterio-venous fistula creation, a statistically significant elevation of blood pressure in common iliac vein and limb overgrowth was observed. Limb enlargement was caused by muscle overgrowth, varicose veins formation and bone elongation. Arterio-venous fistula with proximal outflow limitation led to significant increase of femoral vein circumference and venous wall thickness. Our study indicates that the described rat model mimics major clinical features characteristic for the human Parkes Weber syndrome: presence of arterio-venous fistula, venous hypertension and dilatation, varicose veins formation, and the limb hypertrophy. We reveal that limb overgrowth is caused by bone elongation, muscle hypertrophy, and venous dilatation. The newly established model will permit detailed studies on the mechanisms underlying the disease and on the efficacy of novel therapeutic strategies for the Parkes Weber syndrome treatment.

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

    LENUS (Irish Health Repository)

    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.

  8. BIOCHEMICAL ESTIMATIONS IN 6-HYDROXYDOPAMINE-INDUCED RAT MODEL OF PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Alin Ciobica

    2007-12-01

    OHDA (8µg/4µl was right-unilateral injected in substantia nigra (SN and ventral tegmental area (VTA, and 20 days after neurosurgery the activity of superoxid dismutase (SOD and glutathione peroxidase (GPX from the temporal lobe homogenate was assessed. A significant decrease in both markers was found in the temporal lobe 20 days after neurotoxin administration. These results support that an early event in the course of dopamine depletion following 6-OHDA administration is the generation of oxidative stress.

  9. EGF enhances the effect of GDNF on protecting dopamine neurons in substantia nigra of Parkinson's disease model in rats%表皮生长因子加强胶质细胞系源性神经营养因子对PD模型大鼠黑质多巴胺能神经元的保护作用

    Institute of Scientific and Technical Information of China (English)

    刘洪梅; 丁艳霞; 王炎强; 高殿帅

    2011-01-01

    目的:研究表皮生长因子(EGF)能否加强胶质细胞系源性神经营养因子(GDNF)保护帕金森病(PD)模型大鼠黑质内多巴胺(DA)能神经元.方法:大鼠右侧纹状体内注射6-羟多巴胺(6-OHDA)并行为学分析筛选PD动物模型.将动物模型随机分为EGF+GDNF组(右侧黑质内注射EGF+GDNF)和GDNF组(右侧黑质内注射GDNF).动物继续存活至第21天,取一部分动物中脑黑质节段,用免疫组织化学显色方法,以抗钙结合蛋白D28K(CB)和胶质源纤维酸性蛋白(GFAP)抗体免疫反应阳性分别检测右侧黑质含CB的神经元及激活的星形胶质细胞,光镜下观察并进行细胞计数;另一部分动物被快速断头取脑,分离右侧黑质,用免疫印迹法分析黑质CB及GFAP蛋白的表达,蛋白条带用图像处理仪扫描,结果用LabWorks软件分析处理.结果:免疫组织化学显色显示,EGF+GDNF组大鼠黑质内CB及GFAP反应阳性细胞数量均高于GDNF组;免疫印迹法检测表明EGF+ GDNF组大鼠黑质内CB及GFAP蛋白表达量高于GDNF组.结论:EGF可能通过促进PD模型大鼠黑质内神经元表达CB和激活星形胶质细胞,从而加强GDNF对黑质内DA能神经元的保护作用.%Objective: To explore whether epidermal growth factor (EGF) is capable of enhancing the effect of glial cell line-derived neurotropic factor (GDNF) on protecting dopamine (DA) neurons in substantia nigra (SN) of PD model rats. Methods-. 6-hydroxydopamine (6-OHDA) was injected into rats' right striatum and behavioral tests were performed Parkinson's disease (PD) rats were selected according to the result of behavioral tests. Then, the PD rats were randomly divided into two groups: GDNF group (intranigral GDNF injection) and EGF+GDNF group (intranigral EGF+GDNF injection). The rats were allowed to survive for another 21 days. Then some PD rats were sacrificed, and the midbrain substantia nigra (SN) were performed for analyses of cal-bindin D28 K (CB) and glial fibrillary

  10. Ideal Experimental Rat Models for Liver Diseases.

    Science.gov (United States)

    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

  11. Effects of squalene/squalane on dopamine levels, antioxidant enzyme activity, and fatty acid composition in the striatum of Parkinson's disease mouse model.

    Science.gov (United States)

    Kabuto, Hideaki; Yamanushi, Tomoko T; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2013-01-01

    Active oxygen has been implicated in the pathogenesis of Parkinson's disease (PD); therefore, antioxidants have attracted attention as a potential way to prevent this disease. Squalene, a natural triterpene and an intermediate in the biosynthesis of cholesterol, is known to have active oxygen scavenging activities. Squalane, synthesized by complete hydrogenation of squalene, does not have active oxygen scavenging activities. We examined the effects of oral administration of squalene or squalane on a PD mouse model, which was developed by intracerebroventricular injection of 6-hydroxydopamine (6-OHDA). Squalene administration 7 days before and 7 days after one 6-OHDA injection prevented a reduction in striatal dopamine (DA) levels, while the same administration of squalane enhanced the levels. Neither squalene nor squalane administration for 7 days changed the levels of catalase, glutathione peroxidase, or superoxide dismutase activities in the striatum. Squalane increased thiobarbituric acid reactive substances, a marker of lipid peroxidation, in the striatum. Both squalane and squalene increased the ratio of linoleic acid/linolenic acid in the striatum. These results suggest that the administration of squalene or squalane induces similar changes in the composition of fatty acids and has no effect on the activities of active oxygen scavenging enzymes in the striatum. However, squalane increases oxidative damage in the striatum and exacerbates the toxicity of 6-OHDA, while squalene prevents it. The effects of squalene or squalane treatment in this model suggest their possible uses and risks in the treatment of PD.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    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

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

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O;

    1999-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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. [MAM-E17 schizophrenia rat model].

    Science.gov (United States)

    Kállai, Veronika; Tóth, Attila; Gálosi, Rita; Szabó, Imre; Petykó, Zoltán; Karádi, Zoltán; Kállai, János; Lénárd, László

    2015-01-01

    Schizophrenia is a serious neuropsychiatric disorder. Several brain structures, neurotransmitter systems, genetic and environmental risk factors are suspected in the background. Because of its complexity the mechanism of the disorder is not known exactly, so the treatment of patients is unsolved. In the research of schizophrenia application of the rodent models is widespread. In this study one of these models based on the effect of methylazoxymethanol- acetate (MAM) is described, which is a neurodevelopmental, validated rat model. This antimitotic agent is able to evoke a number of schizophrenic symptomes temporarily disrupting the prenatal neurogenesis. The model reproduces numerous histological and neurophysiological changes of the human disorder, moreover it also represents several behavioral and cognitive phenomena resembling those in schizophrenia. A salient advantage of the model is the demonstration of the diachronic feature of the disorder, that is, postpubertal appearance of the positive symptoms. This model provides widespread opportunities for manipulations of the symptoms, so that using it in the future investigations can lead to a better understanding of this disorder.

  18. Up-regulation of divalent metal transporter 1 in 6-hydroxydopamine intoxication is IRE/IRP dependent.

    Science.gov (United States)

    Jiang, Hong; Song, Ning; Xu, Huamin; Zhang, Shuzhen; Wang, Jun; Xie, Junxia

    2010-03-01

    Iron plays a key role in Parkinson's disease (PD). Increased iron content of the substantia nigra (SN) has been found in PD patients, and divalent metal transporter 1 (DMT1) has been shown to be up-regulated in the SN of both MPTP-induced PD models and PD patients. However, the mechanisms underlying DMT1 up-regulation are largely unknown. In the present study, we observed that in the SN of 6-hydroxydopamine (6-OHDA)-induced PD rats, DMT1 with the iron responsive element (IRE, DMT1+IRE), but not DMT1 without IRE (DMT1-IRE), was up-regulated, suggesting that increased DMT1+IRE expression might account for nigral iron accumulation in PD rats. This possibility was further assessed in an in vitro study using 6-OHDA-treated and DMT1+IRE-over-expressing MES23.5 cells. In 6-OHDA-treated MES23.5 cells, increased iron regulatory protein (IRP) 1 and IRP2 expression was observed, while silencing of IRPs dramatically diminished 6-OHDA-induced DMT1+IRE up-regulation. Pretreatment with N-acetyl-L-cysteine fully suppressed IRPs up-regulation by inhibition of 6-OHDA-induced oxidative stress. Increased DMT1+IRE expression resulted in increased iron influx by MES23.5 cells. Our data provide direct evidence that DMT1+IRE up-regulation can account for IRE/IRP-dependent 6-OHDA-induced iron accumulation initiated by 6-OHDA-induced intracellular oxidative stress and that increased levels of intracellular iron result in aggravated oxidative stress. The results of this study provide novel evidence supporting the use of anti-oxidants in the treatment of PD, with the goal of inhibiting iron accumulation by regulation of DMT1 expression. PMID:20125122

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

    Science.gov (United States)

    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

  20. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    Directory of Open Access Journals (Sweden)

    Kenichiro Sato

    2013-10-01

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

  1. A Rat Excised Larynx Model of Vocal Fold Scar

    Science.gov (United States)

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

    2009-01-01

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

  2. ENU mutagenesis to generate genetically modified rat models

    NARCIS (Netherlands)

    van Boxtel, R.; Gould, M.; Cuppen, E.; Smits, B.M.

    2010-01-01

    The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach f

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

    OpenAIRE

    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 ...

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Dopamine receptor activation promotes adult neurogenesis in an acute Parkinson model

    Science.gov (United States)

    Winner, Beate; Desplats, Paula; Hagl, Christian; Klucken, Jochen; Aigner, Robert; Ploetz, Sonja; Laemke, Jörn; Karl, Alexandra; Aigner, Ludwig; Masliah, Eliezer; Buerger, Erich; Winkler, Jürgen

    2016-01-01

    Cell proliferation of neural progenitors in the subventricular zone (SVZ) of Parkinson disease (PD) patients and animal models is decreased. It was previously demonstrated that the neurotransmitter dopamine modulates cell proliferation in the embryonic brain. The aim of the present study was to analyze whether oral treatment with the dopamine receptor agonist pramipexole (PPX) modulates adult neurogenesis in the SVZ/ olfactory bulb system in a dopaminergic lesion model. 6-Hydroxydopamine (6-OHDA) lesioned adult rats received either PPX (1,0 mg/kg) or PBS orally twice daily and bromodeoxyuridine (BrdU, a cell proliferation marker) for 10 days and were perfused immediately after treatment or 4 weeks after PPX withdrawal. Stereological analysis revealed a significant augmentation in SVZ proliferation by PPX. Consecutively, enhanced neuronal differentiation and more new neurons were present in the olfactory bulb 4 weeks after PPX withdrawal. In addition, dopaminergic neurogenesis was increased in the olfactory bulb after PPX treatment. Motor activity as assessed by using an open field paradigm was permanently increased even after long term PPX withdrawal. In addition, we demonstrate that D2 and D3 receptors are present on adult rat SVZ derived neural progenitors in vitro, and PPX specifically increased mRNA levels of epidermal growth factor receptor (EGF-R) and paired box gene 6 (Pax6). Oral PPX treatment selectively increases adult neurogenesis in the SVZ-olfactory bulb system by increasing proliferation and cell survival of newly generated neurons. Analyzing the neurogenic fate decisions mediated by D2/D3 signaling pathways may lead to new avenues to induce neural repair in the adult brain. PMID:19619535

  7. The LEC rat as a radiosensitive model animal

    International Nuclear Information System (INIS)

    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.)

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

    Institute of Scientific and Technical Information of China (English)

    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. Effects of garlicin on apoptosis in rat model of colitis

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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...

  13. Dietary models for inducing hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Sheyla Leite Matos

    2005-03-01

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

  14. Pioglitazone treatment restores in vivo muscle oxidative capacity in a rat model of diabetes

    NARCIS (Netherlands)

    Wessels, B.; Ciapaite, J.; van den Broek, N. M. A.; Houten, S. M.; Nicolay, K.; Prompers, J. J.

    2015-01-01

    Aim: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. Methods: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The he

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  17. Altered pallido-pallidal synaptic transmission leads to aberrant firing of globus pallidus neurons in a rat model of Parkinson's disease.

    Science.gov (United States)

    Miguelez, Cristina; Morin, Stéphanie; Martinez, Audrey; Goillandeau, Michel; Bezard, Erwan; Bioulac, Bernard; Baufreton, Jérôme

    2012-11-15

    The pattern of activity of globus pallidus (GP) neurons is tightly regulated by GABAergic inhibition. In addition to extrinsic inputs from the striatum (STR-GP) the other source of GABA to GP neurons arises from intrinsic intranuclear axon collaterals (GP-GP). While the contribution of striatal inputs has been studied, notably its hyperactivity in Parkinson's disease (PD), the properties and function of intranuclear inhibition remain poorly understood. Our objective was therefore to test the impact of chronic dopamine depletion on pallido-pallidal transmission. Using patch-clamp whole-cell recordings in rat brain slices, we combined electrical and optogenetic stimulations with pharmacology to differentiate basic synaptic properties of STR-GP and GP-GP GABAergic synapses. GP-GP synapses were characterized by activity-dependent depression and insensitivity to the D(2) receptor specific agonist quinpirole and STR-GP synapses by frequency-dependent facilitation and quinpirole modulation. Chronic dopamine deprivation obtained in 6-OHDA lesioned animals boosted the amplitude of GP-GP IPSCs but did not modify STR-GP transmission and increased the amplitude of miniature IPSCs. Replacement of calcium by strontium confirmed that the quantal amplitude was increased at GP-GP synapses. Finally, we demonstrated that boosted GP-GP transmission promotes resetting of autonomous activity and rebound-burst firing after dopamine depletion. These results suggest that GP-GP synaptic transmission (but not STR-GP) is augmented by chronic dopamine depletion which could contribute to the aberrant GP neuronal activity observed in PD.

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

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

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

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

    Science.gov (United States)

    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

  20. Experimental model of distraction osteogenesis in edentulous rats

    OpenAIRE

    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...

  1. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    OpenAIRE

    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...

  2. Experimental models of hepatic fibrosis in the rat.

    Science.gov (United States)

    Wasser, S; Tan, C E

    1999-01-01

    The rat is a frequently used experimental model in studies involving human disease. We review several methods of inducing hepatic fibrosis and cirrhosis in rats. These include induction by hepatotoxins and hepatocarcinogens such as carbon tetrachloride, dimethylnitrosamine, thioacetamide and furan; the hepatoxin-cum-nutrient, alcohol; a high fat-low choline-low protein diet; immunologic agents such as heterologous serum or bacterial cell wall products; and obstructive jaundice and biliary cirrhosis by common bile duct ligation. PMID:10374036

  3. Novel Rat Model for Neurocysticercosis Using Taenia solium

    Science.gov (United States)

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

    2016-01-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. PMID:26216286

  4. Novel rat model for neurocysticercosis using Taenia solium.

    Science.gov (United States)

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

    2015-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

    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. Detection of visual signals by rats: A computational model

    Science.gov (United States)

    We applied a neural network model of classical conditioning proposed by Schmajuk, Lam, and Gray (1996) to visual signal detection and discrimination tasks designed to assess sustained attention in rats (Bushnell, 1999). The model describes the animals’ expectation of receiving fo...

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D. [Brookhaven National Laboratory, Medical Department, Upton, NY (United States); Morris, G.M. [University of Oxford, Research Institute, Oxford (United Kingdom)

    2000-10-01

    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 (ED{sub 50}) 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)

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

    International Nuclear Information System (INIS)

    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)

  10. ISOLATION OF HEPATIC OVAL CELLS FROM DIFFERENT MODEL RATS INCLUDING DIABETIC RATS

    Institute of Scientific and Technical Information of China (English)

    LU Ying-li; YE Ting-ting; XIA Fang-zhen; WANG Ning-jian; YANG Hua; CHEN Yi

    2009-01-01

    Objective To acquire oval cells (progenitor stem cells) from adult rat liver of different models including diabetic rats. Methods Thirty Sprague-Dawley (SD) rats were divided into 5 groups randomly: control, 2-acetylaminofluorene (2-AAF), 2-AAF+partial hepatectomy (PH), 2-AAF+carbon tetrachloride (CCl4), and diabetic groups. As two-step collagenase perfusion protocol of Seglen, oval cells were isolated by Percoll density gradient centrifugation. Thy1.1 positive cells were sorted by flow cytometry, and then cultured in Dulbeccos minimum Eagles medium (DMEM). Immunofluorescence staining was applied to labelling Thy1.1. Results Different rates of Thy1.1 positive oval cells were found in different rat model groups: 0.5% in 2-AAF, 0.3% in 2-hAAF+PH, 0.2% in 2-AAF+CCl4 , 0.1% in diabetic, and 0.0% in control. Isolated cells adhered to plate with fusiform or polygon as epithelial cells. Conclusion Progenitor stem cells exist in injured liver tissue including those from diabetic rats.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

    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

  13. Comparison of Electroacupuncture in Restrained and Unrestrained Rat Models

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Rat gingival model for testing drugs influencing inflammation

    OpenAIRE

    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...

  16. Development of Wistar rat model of insulin resistance

    Institute of Scientific and Technical Information of China (English)

    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.

  17. Palmitoyl Serotonin Inhibits L-dopa-induced Abnormal Involuntary Movements in the Mouse Parkinson Model.

    Science.gov (United States)

    Park, Hye-Yeon; Ryu, Young-Kyoung; Go, Jun; Son, Eunjung; Kim, Kyoung-Shim; Kim, Mee Ree

    2016-08-01

    L-3,4-dihydroxyphenylalanine (L-DOPA) is the most common treatment for patients with Parkinson's disease (PD). However, long term use of L-DOPA for PD therapy lead to abnormal involuntary movements (AIMs) known as dyskinesia. Fatty acid amide hydrolase (FAAH) is enriched protein in basal ganglia, and inhibition of the protein reduces dyskinetic behavior of mice. Palmitoyl serotonin (PA-5HT) is a hybrid molecule patterned after arachidonoyl serotonin, antagonist of FAAH. However, the effect of PA-5HT on L-DOPA-induced dyskinesia (LID) in PD have not yet been elucidated. To investigate whether PA-5HT relieve LID in PD and decrease hyperactivation of dopamine D1 receptors, we used the 6-hydroxydopomine (6-OHDA)-lesioned mouse model of PD and treated the L-DOPA (20 mg/kg) for 10 days with PA-5HT (0.3 mg/kg/day). The number of wall contacts with the forelimb in the cylinder test was significantly decreased by 6-OHDA lesion in mice and the pharmacotherapeutic effect of L-DOPA was also revealed in PA-5HT-treated mice. Moreover, in AIMs test, PA-5HT-treated mice showed significant reduction of locomotive, axial, limb, and orofacial AIMs score compared to the vehicle-treated mice. LID-induced hyper-phosphorylation of ERK1/2 and overexpression of FosB/ΔFosB was markedly decreased in 6-OHDA-lesioned striatum of PA-5HT-treated mice, indicating that PA-5HT decreased the dopamine D1 receptor-hyperactivation induced by chronic treatment of L-DOPA in dopamine-denervated striatum. These results suggest that PA-5HT effectively attenuates the development of LID and enhance of ERK1/2 phosphorylation and FosB/ΔFosB expression in the hemi-parkinsonian mouse model. PA-5HT may have beneficial effect on the LID in PD.

  18. Formation of a reliable capsular flap in a rat model.

    NARCIS (Netherlands)

    Schuringa, M.C.; Hartman, E.H.M.; Ruhe, P.Q.; Jansen, J.A.; Spauwen, P.H.M.

    2007-01-01

    Prefabrication can be used to produce capsular flaps; other researchers have confirmed the feasibility of such flaps. Before the possibilities of capsular flaps can be explored, a reliable method to create these flaps has to be established first. METHODS: To produce capsular flaps in a rat model, th

  19. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    Directory of Open Access Journals (Sweden)

    William W. Lao, MD

    2014-04-01

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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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 ...

  3. Establishment of novel rat models for premalignant breast disease

    Institute of Scientific and Technical Information of China (English)

    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.

  4. Experimental model of heterotopic ossification in Wistar rats

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

    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...

  6. Molecular mechanism of icariin on rat asthmatic model

    Institute of Scientific and Technical Information of China (English)

    XU Chang-qing; LE Jing-jing; DUAN Xiao-hong; DU Wei-jing; LIU Bao-jun; WU Jing-feng; CAO Yu-xue; DONG Jing-cheng

    2011-01-01

    Background Effects of icariin on airway inflammation in asthmatic rats and the intervention of LPS induced inflammation are interfered with the machanism of icariin. Our study aimed to observe the effect of icariin on ovalbumin-induced imbalance of Th1/Th2 cytokine expression and its mechanism.Methods Sixty male SD rats were randomly divided into control group (PBS), asthma group (ovalbumin (OVA)-induced),dexamethasone group, and OVA+icariin low, medium and high dose groups (5, 10, 20 mg/kg, respectively). Each group had ten rats. The model of OVA sensitization was a rat asthma model. Enzyme-linked immunosorbent assay (ELISA)method was used to observe the effects of icariin on interleukin-4 (IL-4) and inerferon Y (IFN-Y) in rats' lung tissue.Immunohistochemical staining was applied to detect the intervention effects of icariin on T cells (T-bet) and gatabinding protein 3 (GATA-3) in rat pulmonary tissue. Realtime RT-PCR was used to observe the intervention effects of icariin on T-bet and GATA-3 mRNA expression in rat pulmonary tissue and spleen lymphocytes. Western blotting was used to observe the icariin intervention effects on T-bet, GATA-3 and nuclear factor-Kappa B (NF-κB) p65 protein expressions in rat pulmonary tissue.Results The ELISA results from pulmonary tissue showed that IL-4 expression was significantly reduced (P <0.05),while the IFN-y expression increased but not significantly when we compared OVA+icariin medium and high dose groups with the asthma group. Immunohistochemical staining of pulmonary tissue showed that the GATA-3 decreased significantly while the T-bet staining did not change in the OVA+icariin high dose group. In pulmonary tissue and spleen lymphocytes T-bet and GATA-3 mRNA expressions were significantly reduced (P <0.05) in icariin treatment groups compared with the asthma model group. GATA-3 and T-bet mRNA in rat spleen lymphocytes in the asthma group were higher than in the control group. GATA-3 mRNA expression in pulmonary

  7. Experimental model of distraction osteogenesis in edentulous rats

    Directory of Open Access Journals (Sweden)

    Maria Montserrat Pujadas Bigi

    2011-06-01

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

  8. A chronic ulcerative colitis model in rats

    Institute of Scientific and Technical Information of China (English)

    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.

  9. Rat gingival model for testing drugs influencing inflammation

    Directory of Open Access Journals (Sweden)

    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. Combating Combination of Hypertension and Diabetes in Different Rat Models

    Directory of Open Access Journals (Sweden)

    Talma Rosenthal

    2010-03-01

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

  11. Methodological characteristics in establishing rat models of poststroke depression

    Institute of Scientific and Technical Information of China (English)

    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

  12. The inhibition of nanog gene transfer on the inflammatory reaction induced by microglial cell in Parkinson disease rats%转nanog基因抑制帕金森病大鼠脑内小胶质细胞介导的炎性反应

    Institute of Scientific and Technical Information of China (English)

    陈施艳; 张志坚; 刘丽金; 林红; 吴秀丽; 王伟; 王志强

    2014-01-01

    目的 探讨转nanog基因对6-羟多巴胺(6-OHDA)诱导的帕金森病大鼠中脑黑质区小胶质细胞的激活及肿瘤坏死因子α(TNF-α)表达的影响.方法 将大鼠随机分为对照、6-OHDA+ PBS、6-OHDA+ PNL与6-OHDA+nanog组.模型组大鼠左侧纹状体内注射6-OHDA,再将PBS、慢病毒空载体PNL-IRES.EGFP (PNL)、转nanog基因载体分别注入6-OHDA+ PBS、6-OHDA+ PNL与6-OHDA+ nanog组大鼠左侧纹状体;14 d后,注射阿朴吗啡(APO),观察大鼠的旋转行为;免疫组织化学染色观察黑质多巴胺能神经元数量;免疫荧光观测黑质区小胶质细胞数量及TNF-α表达.结果 注射后14 d,6-OHDA+ nanog组大鼠APO诱发的旋转效应低于6-OHDA+ PNL与6-OHDA+PBS组(P<0.05);模型组注射侧黑质多巴胺能神经元数量较对照组明显减少(P<0.05),但6-OHDA+ nanog组存活的多巴胺能神经元数量多于6-OHDA+ PNL与6-OHDA+ PBS组(P<0.05).模型组大鼠注射侧黑质区小胶质细胞数量和TNF-α表达均较对照组增加(P<0.05),但6-OHDA+ nanog组小胶质细胞数目和TNF-α表达水平低于6-OHDA+ PNL与6-OHDA+ PBS组(P<0.05).结论 转nanog基因可抑制帕金森病大鼠脑内小胶质细胞活化介导的炎性反应,具有神经元保护作用.

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

    Science.gov (United States)

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

  14. Chronic gastritis rat model and role of inducing factors

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Ventricular repolarization in a rat model of global heart failure.

    Science.gov (United States)

    Krandycheva, Valeria; Kharin, Sergey; Strelkova, Marina; Shumikhin, Konstantin; Sobolev, Aleksey; Shmakov, Dmitry

    2013-07-01

    Isoproterenol in high doses induces infarction-like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol-induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation-recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation-recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation-recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. A rat model for embolic encephalitis

    DEFF Research Database (Denmark)

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

    2011-01-01

    -brain-barrier. This provides our model with several advantages: minimized surgical intervention, bacteria gain access to the brain by the circulation and, no foreign materials are implated in the brain. We thereby mirror the human scenario in several ways: 1: Cerebral infarction by thrombosis or disseminated intravascular...... coagulation is a key mechanism involved in neurologic complications to human bacteriaemia. 2: Human brain abscesses are primarily located in the same anatomical area that we target in our model. Our model therefore offers a tool for several scientific areas within research of brain infection and inflammation....

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

    Science.gov (United States)

    Vieira, Vilberto J; D'Acampora, Armando; Neves, Fernanda S; Mendes, Paulo R; Vasconcellos, Zulmar A DE; Neves, Rodrigo D'Eça; Figueiredo, Claudia P

    2016-09-01

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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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....

  1. Culture Model of Rat Portal Myofibroblasts

    Science.gov (United States)

    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. Ideal Experimental Rat Models for Liver Diseases

    OpenAIRE

    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...

  3. An improved experimental model for peripheral neuropathy in rats

    Directory of Open Access Journals (Sweden)

    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.

  4. An improved experimental model for peripheral neuropathy in rats

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-15

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

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

    Science.gov (United States)

    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

  6. Expression of recombinant human erythropoietin pretreatment on inflammatory factors derived from glial cell in rats with Parkinson disease%重组人促红细胞生成素预处理对帕金森病大鼠胶质细胞源性炎症因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    罗常月

    2012-01-01

    目的 探讨重组人促红细胞生成素(rhEPO)预处理对帕金森病(PD)大鼠胶质细胞源性炎症因子表达的影响.方法 40只SD大鼠随机分为4组,A组:右侧纹状体内注射rhEPO 24h后,同侧黑质内注射6-羟基多巴胺(6-OHDA);B组:右侧纹状体内立体定向注射与rhEPO等量的生理盐水,24h后同侧黑质内立体定向注射6-OHDA;C组:右侧黑质内立体定向注射6-OHDA;D组:右侧黑质内立体定向注射与6-OHDA等量的生理盐水.4周后采用酶联免疫吸附法检测血清诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子(TNF)-α含量;逆转录(RT)-PCR法检测黑质iNOS和TNF-α mRNA的表达.结果 与D组比较,A、B、C组大鼠血清iNOS、TNF-α含量增多,黑质iNOS、TNF-α mRNA表达增高(均P<0.05);与B组和C组比较,A组大鼠血清iNOS、TNF-α含量显著减少,黑质iNOS、TNF-α mRNA表达显著降低(均P<0.05).结论 rhEPO可能通过抑制黑质TNF-α、iNOS表达,减轻6-OHDA对多巴胺能神经元的毒性损害,具有神经保护作用.%Objective To explor the expression of recombinant human erythropoietin (rhEPO) pretreatment on inflammatory factors derived from glial cell in rats with Parkinson disease ( PD ). Methods Forty SD rats were randomly divided into 4 groups. A group: After 24 h of rhEPO injected in right striatum,6-hydroxydopamine (6-OHDA) was iniected in ipsilatcral substantia nigra (SN) ;B group: Aftcr 24 h of normal saline(NS, same amount of rhEPO) injected in right striatum,6-OHDA was injected in ipsilateral SN;C group:6-0HDA was injected in right SN; D group: NS ( same amount of 6-OHDA) was injected in right SN. Four weeks later, the levels of serum tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS) were examined by enzyme linked immuno sorbent assay (ELISA). The expression of TNF-α mRNA and iNOS mRNA in SN were detected by reverse transcription (RT)-PCR. Results Compared with D group,the levels of serum of iNOS, TNF-a and the

  7. Aerosol Infection Model of Tuberculosis in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Sheshagiri Gaonkar

    2010-01-01

    Full Text Available We explored suitability of a rat tuberculosis aerosol infection model for investigating the pharmacodynamics of new antimycobacterial agents. Infection of rats via the aerosol route led to a reproducible course of M. tuberculosis infection in the lungs. The pulmonary bacterial load increased logarithmically during the first six weeks, thereafter, the infection stabilized for the next 12 weeks. We observed macroscopically visible granulomas in the lungs with demonstrable acid-fast bacilli and associated histopathology. Rifampicin (RIF at a dose range of 30 to 270 mg/kg exhibited a sharp dose response while isoniazid (INH at a dose range of 10 to 90 mg/kg and ethambutol (EMB at 100 to 1000 mg/kg showed shallow dose responses. Pyrazinamide (PZA had no dose response between 300 and 1000 mg/kg dose range. In a separate time kill study at fixed drug doses (RIF 90 mg/kg, INH 30 mg/kg, EMB 300 mg/kg, and PZA 300 mg/kg the bactericidal effect of all the four drugs increased with longer duration of treatment from two weeks to four weeks. The observed infection profile and therapeutic outcomes in this rat model suggest that it can be used as an additional, pharmacologically relevant efficacy model to develop novel antitubercular compounds at the interface of discovery and development.

  8. Standardization of model to induce obesity in rats

    Directory of Open Access Journals (Sweden)

    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. Unilateral Ibotenic Acid Lesions of the Prefrontal Cortex Reduce

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Characterization of an animal model of postmenopausal hypertension in spontaneously hypertensive rats.

    Science.gov (United States)

    Fortepiani, Lourdes A; Zhang, Huimin; Racusen, Lorraine; Roberts, L Jackson; Reckelhoff, Jane F

    2003-03-01

    Blood pressure (BP) increases in postmenopausal women. The mechanisms responsible are unknown. The present study was performed to characterize a model of postmenopausal hypertension in the rat and to determine the role that oxidative stress may play in mediating the postmenopausal hypertension. Spontaneously hypertensive rats were ovariectomized (ovx) or left intact (PMR) at 8 months and were aged to 18 months. These animals were compared with young females (YF; 4 or 8 months of age) and old males (18 months) for some measurements. Estradiol levels were decreased in PMR rats to levels not different from YF rats in proestrous or from old males. BP increased progressively with age in PMR rats but not in ovx or male rats, such that the gender difference in hypertension disappeared by 18 months. Glomerular filtration rate was lower in ovx and PMR rats than in YF rats. Renal plasma flow and renal vascular resistance were similar between YF and ovx rats, but lower and higher, respectively, in PMR rats. Serum testosterone increased by 60% in ovx rats and 400% in PMR rats compared with YF rats. Plasma renin activity also increased in PMR rats but not in ovx rats. Chronic treatment (for 8 months beginning at 8 months of age) of PMR rats with vitamins E and C, but not tempol, resulted in a significant reduction in BP and excretion of F2-isoprostanes. In contrast, tempol, but not vitamins E and C, reduced BP in old males. These data suggest that the PMR rats, but not ovx rats, may be a suitable model for the study of postmenopausal hypertension, and that oxidative stress plays a role in the increased BP.

  12. Modeling the mechanical properties of liver fibrosis in rats.

    Science.gov (United States)

    Zhu, Ying; Chen, Xin; Zhang, Xinyu; Chen, Siping; Shen, Yuanyuan; Song, Liang

    2016-06-14

    The progression of liver fibrosis changes the biomechanical properties of liver tissue. This study characterized and compared different liver fibrosis stages in rats in terms of viscoelasticity. Three viscoelastic models, the Voigt, Maxwell, and Zener models, were applied to experimental data from rheometer tests and then the elasticity and viscosity were estimated for each fibrosis stage. The study found that both elasticity and viscosity are correlated with the various stages of liver fibrosis. The study revealed that the Zener model is the optimal model for describing the mechanical properties of each fibrosis stage, but there is no significant difference between the Zener and Voigt models in their performance on liver fibrosis staging. Therefore the Voigt model can still be effectively used for liver fibrosis grading. PMID:27017300

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

    Institute of Scientific and Technical Information of China (English)

    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.

  14. Stem cell therapy in intracerebral hemorrhage rat model

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Research of combined liver-kidney transplantation model in rats

    Institute of Scientific and Technical Information of China (English)

    Jiageng Zhu; Jun Li; Ruipeng Jia; Jianghao Su; Mingshun Shen; Zhigang Cao

    2007-01-01

    Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.

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

    Directory of Open Access Journals (Sweden)

    K. M. Rice

    2014-01-01

    Full Text Available 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 humans. To compound the complication of aging gender has also been indicated as a risk factor for various cardiovascular diseases. This review addresses the systemic pathophysiology of the cardiovascular system associated with aging and gender for aging research with regard to the applicability of rat derived data for translational application to human aging.

  17. A rat model with an isolated bladder in situ

    DEFF Research Database (Denmark)

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

    1997-01-01

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    gain access to the brain by the circulation and, no foreign materials other than bacteria are implated in the brain. This ensures high face-validity and high construct-validity of the model for three reasons: 1) Cerebral infarction by thrombosis or disseminated intravascular coagulation is a key......µl thrombin (2.5 IU/ml) in a catheter until coagulated. A sterile fibrin-clot of 5 mm was selected for embolization and injected via the ECA catheter. The common carotid artery was clamped during injection thereby directing the embolus via the internal carotid artery to the brain. The clot...

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

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

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

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

    OpenAIRE

    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...

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

    Institute of Scientific and Technical Information of China (English)

    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. Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal.

    Science.gov (United States)

    Carli, M; Robbins, T W; Evenden, J L; Everitt, B J

    1983-09-01

    Five experiments examined the effects of destruction of the dorsal noradrenergic bundle (DNAB), arising in the locus coeruleus, both on brightness and spatial visual discrimination, and selective attention. An analogue o Leonard's 5-choice serial reaction task for human subjects was used. Hungry rats were trained to detect brief (0.5 sec) flashes of light presented randomly in one of 5 locations with a fixed intertrial interval of 5 sec, paced by the rat. Correct responses were rewarded with food and incorrect responses punished by time-out (darkness + delay). Following training to high levels of accuracy (80%, with less than 20% errors of omission), rats received either 6-OHDA (4 micrograms/2 microliters) injected bilaterally into the trajectory of the dorsal bundle, or injection of vehicle (0.1% ascorbic acid in 0.9% saline). The 6-OHDA lesion was sufficient to reduce cortical NA by 84%. Performance on both the spatial discrimination and brightness (produced by graded reductions in the brightness of the stimuli) discrimination was unaffected by DNAB lesions. However, the DNAB lesion produced significant decreases in accuracy and increases in omissions when the stimuli were presented at faster, unpredictable rates. In addition, although intense white noise failed to produce differential impairments when presented simultaneously with the visual discriminanda, the DNAB lesion significantly impaired accuracy when the noise was presented immediately prior to, but not overlapping, the onset of the visual stimuli. The implications of this pattern of deficits in performance found following DNAB lesions is discussed in terms of disruptive effects of cortical NA depletion upon mechanisms of selective attention and arousal. PMID:6639741

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    Ying Zhang

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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  7. Triptolide ameliorates colonic fibrosis in an experimental rat model.

    Science.gov (United States)

    Tao, Qingsong; Wang, Baochai; Zheng, Yu; Li, Guanwei; Ren, Jianan

    2015-08-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn's disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly repeated administration with a low-dose of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and was then treated with triptolide or PBS daily (control) simultaneously. Extracellular matrix (ECM) deposition in the colon was examined with image analysis of Masson Trichrome staining. Total collagen levels in colonic homogenates were measured by a Sircol assay. Collagen Iα1 transcripts and collagen I protein were measured ex vivo in the isolated colonic subepithelial myofibroblasts by reverse transcription-quantitative polymerase chain reaction and immunoblot analysis, respectively. The results indicated that triptolide decreased ECM deposition and collagen production in the colon, and inhibited collagen Iα1 transcripts and collagen I protein expression in the isolated subepithelial myofibroblasts of the rats with colonic fibrosis. In conclusion, triptolide ameliorates colonic fibrosis in the experimental rat model, suggesting triptolide may be a promising compound for inflammatory bowel disease treatment. PMID:25845760

  8. Transplanted Neural Stem Cells: Playing a Neuroprotective Role by Ceruloplasmin in the Substantia Nigra of PD Model Rats?

    Science.gov (United States)

    Xiao, Jia-Jia; Yin, Ming; Wang, Ze-Jian; Wang, Xiao-Ping

    2015-01-01

    Although mounting evidence suggests that ceruloplasmin (CP) deficiency and iron deposition are pivotal factors responsible for exacerbating demise of dopaminergic neurons in the substantia nigra (SN) of the Parkinsonism and neural stem cells (NSCs) are believed to be excellent candidates for compensating the lost dopaminergic neurons, there are few researches to explore the change of CP expression and of iron deposition in the pathological microenvironment of SN after NSCs transplantation and the ability of grafted NSCs to differentiate directionally into dopaminergic neurons under the changed homeostasis. With substantia nigral stereotaxic technique and NSCs transplantation, we found that tyrosine hydroxylase and CP expression decreased and iron deposition increased in the lesioned SN after 6-OHDA administration compared with control, while tyrosine hydroxylase and CP expression increased and iron deposition decreased after NSCs transplantation compared to 6-OHDA administration alone. Only a small number of embedding NSCs are able to differentiate into dopaminergic neurons. These results suggest that grafted NSCs have an influence on improving the content of CP expression, which may play a neuroprotective role by decreasing iron deposition and ameliorating damage of dopaminergic neurons and possibly underline the iron-related common mechanism of Parkinson's disease and Wilson's disease.

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

    International Nuclear Information System (INIS)

    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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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)

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-12-01

    The use of exercise to minimize doxorubicin (DOX)-induced cardiotoxicity is gaining attention. However, very few clinically relevant reports exist investigating the effects of exercise performed during and following DOX treatments. The purpose of this study, therefore, was to examine the effects of voluntary wheel running during and following DOX treatment using two models of late-onset DOX cardiotoxicity in the rat. Female Sprague-Dawley rats received either DOX or saline injections using one of two separate treatment regimens. These regimens involved either daily or weekly DOX injections with cumulative doses for both protocols totaling 15 mg/kg. Daily DOX injections were 1 mg/kg and lasted for 15 consecutive days while weekly DOX injections were 2.5 mg/kg and lasted for six consecutive weeks with control animals receiving matched saline injection regimens. Immediately following the initial DOX/saline injection, animals were randomly housed in cages with voluntary running wheels or standard rat cages throughout DOX/saline treatments and continued until reaching 10 weeks. Cardiac function was then assessed using echocardiography and an isolated working heart model, and myosin heavy chain (MHC) isoform distribution was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When compared wth controls, daily DOX treatment resulted in reduced running wheel distances at weeks 2-10 (P 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

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

    Directory of Open Access Journals (Sweden)

    Tufi Neder Meyer

    1998-10-01

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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

    Science.gov (United States)

    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. EFECTO DE LA ADMINISTRACIÓN INTRACEREBRAL DE MK-801 Y (- NICOTINA EN LAS CONCENTRACIONES EXTRACELULARES DE GLU Y GABA EN EL NÚCLEO PEDUNCULOPONTINO DE RATAS Effect of the Mk801 and (- Nicotine Intracerebral Administration on Glu and Gaba Extracellular Concentration in the Pedunculopontine Nucleus from Rats

    Directory of Open Access Journals (Sweden)

    LISETTE BLANCO LEZCANO

    Full Text Available Aunque la manipulación farmacológica de los sistemas glutamatérgico y colinérgico se ha tratado en modelos experimentales de enfermedad de Parkinson (EP, pocos autores han realizado estudios de esta temática a nivel del núcleo pedunculopontino (NPP. El presente trabajo aborda los cambios en las concentraciones extracelulares (CE de glutamato (Glu y ácido δ-amino butírico (GABA en el NPP de ratas hemiparkinsonizadas por inyección de 6-hidroxidopamina (6-OHDA y sometidas a infusión local de MK-801 (10 µmol/L o (- nicotina (10 mM. La infusión se realizó mediante microdiálisis cerebral y la determinación de CE de neurotransmisores se realizó a través de cromatografía líquida de alta resolución acoplada a detección de fluorescencia. La infusión de MK-801 en el NPP produjo disminución significativa de CE de Glu (pAlthough the pharmacological manipulation of the glutamatergic and cholinergic systems have been studied in animal models of Parkinson´s disease (PD, only some authors have done work on this topic at the pedunculopontine nucleus (PPN. The present work studied the changes in glutamate (Glu and δ-aminobutyric acid (GABA extracellular concentrations (EC in the PPN from hemiparkinsonian rats by 6hydroxydopamine injection. The rats were locally perfused by MK-801 (10 µmol/L or (- nicotine (10 mM solutions by cerebral microdyalisis. The biochemical studies were carried out through high performance liquid chromatography coupled to fluorescence detection. MK-801 infusion induced a significant decrease of Glu (p< 0.01 and GABA (p< 0.01 EC in PPN. On the other hand (- nicotine infusion induced a significant increase of Glu (p< 0.001 and GABA (p< 0.001 EC in PPN from hemiparkinsonian rats. The local blockade of NMDA receptors by MK-801 infusion facilitates the interaction between Glu and their metabotropic receptors that take part in presynaptic inhibition mechanisms and interfere with neurotransmitters release. Meanwhile, the

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-24

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

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

    OpenAIRE

    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.

  7. Protective effect of Mrh-aFGF on the neurons in ventral tegmental area of rats with Parkinson’ s disease%Mrh-aFGF对帕金森病大鼠中脑腹侧被盖区神经元的保护

    Institute of Scientific and Technical Information of China (English)

    肖春苟; 蒋威; 李力强; 邹锦慧; 沈伟哉

    2016-01-01

    Objepctive To explore the protective effect of modified recombinant human aFGF ( Mrh-aFGF) on the neurons in ventral tegmental area of rats with Parkinson’ s disease ( PD) . Methods The 54 SD rats were ramdomly divided into the control group,the model group and the treatment group,and there were 18 rats in each group. PD rats of the model group and the treatment group were induced by in-jecting 6-OHDA into the left substantia nigra compacta ( SNC) and ventral tegmental area ( VTA) to build the PD model. Rats in the treat-ment group were given Mrh-aFGF injection after lateral ventricle injection,and the behavioral changes of the rats were detected after apomor-phine injection. The morphologic features and pathological changes of neurons in the ventral tegmental area were observed by Nissl’ s staining and electronic microscope. Results Compared to the right VTA of PD rats,the number of neurons in left side ( the injured side) decreased significantly in the model group(P<0. 05). In the treatment group,the structure of left (the injured side) VTA was markedly improved and the number of neurons was increased one week,two weeks and four weeks after operation compared with the model group (P<0. 05). The neurons in the VTA of the model group were found to have karyopyknosis,endoplasmic reticulum,degranulation,mitochondria swelling,cristae disappear,pre-synaptic and post-synaptic membranes swelling,and synaptic cleft disappear. In the treatment group,the ultrastructure of the neurons in the VTA,such as nuclei,mitochondria,synaptic structure,kept well compared to the model group. Conclusion Mrh-aFGF could protect the neurons in the ventral tegmental area from the loss and improve the ultrastructure of the neurons of PD rats.%目的:探讨重组人改构体酸性成纤维细胞生长因子( Mrh-aFGF)对帕金森病( PD)大鼠中脑腹侧被盖区神经元病变的影响。方法将54只SPF级雄性SD大鼠随机分为对照组、模型组和治疗组,每组18只。6-

  8. Description of “Tail Suspension” as a Model of ‹mmobilization in Rats

    Directory of Open Access Journals (Sweden)

    Ayçe Atalay

    2002-09-01

    Full Text Available Since human beings have included outer space to their living places, effects of gravity on bone has been extensively studied. Authors claim that basic biologic mechanisms are similar in rats and human so rats should serve as a useful model for studying osteoporosis. Models for simulating microgravity conditions can be grouped into two as local and systemic models. We aimed to summarize models for immobilization as well as detailed description of tail suspension model.

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

    Institute of Scientific and Technical Information of China (English)

    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 ...

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

    DEFF Research Database (Denmark)

    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, predomi......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...

  11. Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

    Institute of Scientific and Technical Information of China (English)

    Cuiping Yang; Changchun Cai; Xiaojin Yang; Yanping Yang; Zhigang Zhou; Jianhua Liu; Heping Ye; Hongjiao Wan

    2012-01-01

    An experimental model of schizophrenia was established using dizocilpine (MK-801). Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Zinc supplementation decreases hepatic copper accumulation in LEC rat: a model of Wilson's disease.

    Science.gov (United States)

    Gonzalez, Blanca P Esparza; Niño Fong, Rodolfo; Gibson, Candace J; Fuentealba, I Carmen; Cherian, M George

    2005-01-01

    The effect of dietary zinc (Zn) supplementation on copper (Cu)-induced liver damage was investigated in Long-Evans Cinnamon rats (LEC), a model for Wilson's disease (WD). Four-week-old LEC (N=64) and control Long-Evans (LE) (N=32) female rats were divided into two groups; one group was fed with a Zn-supplemented diet (group I) and the other was given a normal rodent diet (group II). LEC rats were killed at 6, 8, 10, 12, 18, and 20 wk of age; the LE control rats were killed at 6, 12, 18, and 20 wk of age. Cu concentration in the liver was reduced in LEC rats fed the Zn-supplemented diet compared with LEC rats on the normal diet between 6 and 18 wk of age. Metallothionein (MT) concentration in the livers of LEC rats in group I increased between 12 and 20 wk of age, whereas hepatic MT concentration in LEC rats from group II decreased after 12 wk. Hepatocyte apoptosis, as determined by TUNEL, was reduced in Zn-supplemented LEC rats at all ages. Cholangiocellular carcinoma was observed only in LEC rats in group II at wk 20. These results suggest that Zn supplementation can reduce hepatic Cu concentration and delay the onset of clinical and pathological changes of Cu toxicity in LEC rats. Although the actual mechanism of protection is unknown, it could be explained by sequestration of dietary Cu by intestinal MT, induced by high dietary Zn content.

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

    Science.gov (United States)

    2016-01-01

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Salvatore eMagara

    2015-04-01

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

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  19. Causes of immune dysfunction in hyperbilirubinemia model rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-Min Sun; Ping Kang; Ke Tao

    2015-01-01

    Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods: A total of 60 newborn SD rats were equally randomized into normal saline (NS) group, LPS control group, bilirubin control group, low-dose group and high-dose group. After anesthesia, 0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups; 1 h later, the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups. After 5 or 24 hours of model establishment, spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method. After 24 hours of model establishment, serum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results: In contrast to low-dose bilirubin, high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS. After 5 hours of model establishment, compared with NS group, MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced (P<0.05). In high-dose group, inflammotory factors levels and CD8+ T cells percentage were all higher than LPS control and NS group (P<0.05), while CD4+ T cells percentage was lower than NS group (P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF-κB signal pathways activation and aggravate inflammatory reaction, thus caused immunosuppression with inflammation cascade, which resulted in the immune dysfunction.

  20. The comparison of immobility time in experimental rat swimming models.

    Science.gov (United States)

    Calil, Caroline Morini; Marcondes, Fernanda Klein

    2006-09-27

    Rat swimming models have been used in studies about stress and depression. However, there is no consensus about interpreting immobility (helplessness or adaptation) in the literature. In the present study, immobility time, glucose and glycogen mobilization, corticosterone and the effect of desipramine and diazepam were investigated in two different models: swimming stress and the forced swimming test. Immobility time was lower in swimming stress than in the forced swimming test. Both swimming models increased corticosterone levels in comparison with control animal levels. Moreover, swimming stress induced higher corticosterone levels than the forced swimming test did [F(2,14)=59.52; pswimming stressswimming testswimming stress in comparison with the forced swimming test and control. The immobility time was recorded and measured in another group treated with desipramine and diazepam in two protocols: a single session of forced swimming test or swimming stress and two sessions (pre- and retest) of forced swimming model or swimming stress. Desipramine decreased the immobility time in the forced swimming test in both the single [F(2,25)=20.63; pswimming session, without changes in the swimming stress model. Diazepam increased the immobility time in the swimming stress but not in the forced swimming test during the single [F(2,26)=11.24; p=0.0003] and retest sessions [F(2,38)=4.17; p=0.02]. It was concluded that swimming stress and the forced swimming test induced different behavior, hormonal and metabolic responses and represented different situations to the animal.

  1. Wnt Pathway Activation in Long Term Remnant Rat Model

    Directory of Open Access Journals (Sweden)

    E. Banon-Maneus

    2014-01-01

    Full Text Available Progression of chronic kidney disease (CKD is characterized by deposition of extracellular matrix. This is an irreversible process that leads to tubulointerstitial fibrosis and finally loss of kidney function. Wnt/β-catenin pathway was reported to be aberrantly activated in the progressive damage associated with chronic organ failure. Extensive renal ablation is an experimental model widely used to gain insight into the mechanisms responsible for the development of CKD, but it was not evaluated for Wnt/β-catenin pathway. This study aimed to elucidate if the rat 5/6 renal mass reduction model (RMR is a good model for the Wnt/β-catenin activation and possible next modulation. RMR model was evaluated at 12 and 18 weeks after the surgery, when CKD is close to end-stage kidney disease demonstrated by molecular and histological studies. Wnt pathway components were analyzed at mRNA and protein level. Our results demonstrate that Wnt pathway is active by increase of β-catenin at mRNA level and nuclear translocation in tubular epithelium as well as some target genes. These results validate the RMR model for future modulation of Wnt pathway, starting at shorter time after the surgery.

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

    Science.gov (United States)

    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...

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  7. Zuogui pills for myelinolysis in a rat model of experimental autoimmune encephalomyelitis

    Institute of Scientific and Technical Information of China (English)

    Yongping Fan; Kelong Chen; Kangning Li; Jianping Zhou; Yan Shao; Hongyan Liu; Wenjing Yang

    2011-01-01

    Zuogui pills have been shown to attenuate the inflammatory reaction in a rat model of experimental autoimmune encephalomyelitis (EAE). The present study attempted to investigate the pathology underlying the influence of Zuogui pills on myelinolysis in EAE rats. Hematoxylin-eosin and Luxol fast blue staining showed that the myelinolysis foci in the cerebrum, cerebellum, brain stem, and the spinal cord of EAE rats were significantly decreased, along with serum myelin basic protein content following treatment with Zuogui pills.

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  14. A rat uterine horn model of genital tract wound healing.

    Science.gov (United States)

    Schlaff, W D; Cooley, B C; Shen, W; Gittlesohn, A M; Rock, J A

    1987-11-01

    A rat uterine horn model of genital tract wound healing is described. Healing was reflected by acquisition of strength and elasticity, measured by burst strength (BS) and extensibility (EX), respectively. A tensiometer (Instron Corp., Canton, MA) was used to assess these characteristics in castrated and estrogen-supplemented or nonsupplemented animals. While the horn weights (HW), BS, and EX of contralateral horns were not significantly different, the intra-animal variation of HW was 7.2%, BS was 17.7% and EX was 38.2%. In a second experiment, one uterine horn was divided and anastomosed, and the animal given estrogen supplementation or a placebo pellet. Estrogen administration was found to increase BS and EX of anastomosed horns prior to 14 days, but had no beneficial effect at 21 or 42 days. The data suggest that estrogen may be required for optimal early healing of genital tract wounds.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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...

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

    OpenAIRE

    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,...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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....

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    , namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization...

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

    Directory of Open Access Journals (Sweden)

    Yingli Jin

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    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)

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Bernhard Kraemer

    2014-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Chengbai Liang

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

  14. Neuromodulation attenuates bladder hyperactivity in a rat cystitis model

    OpenAIRE

    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...

  15. Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: involvement of hydrogen peroxide-dependent and -independent action.

    Science.gov (United States)

    Saito, Yoshiro; Nishio, Keiko; Ogawa, Yoko; Kinumi, Tomoya; Yoshida, Yasukazu; Masuo, Yoshinori; Niki, Etsuo

    2007-03-01

    The neurotoxin 6-hydroxydopamine (6-OHDA) has been widely used to generate an experimental model of Parkinson's disease. It has been reported that reactive oxygen species (ROS), such as the superoxide anion and hydrogen peroxide (H2O2), generated from 6-OHDA are involved in its cytotoxicity; however, the contribution and role of ROS in 6-OHDA-induced cell death have not been fully elucidated. In the present study using PC12 cells, we observed the generation of 50 microM H2O2 from a lethal concentration of 100 microM 6-OHDA within a few minutes, and compared the sole effect of H2O2 with 6-OHDA. Catalase, an H2O2-removing enzyme, completely abolished the cytotoxic effect of H2O2, while a significant but partial protective effect was observed against 6-OHDA. 6-OHDA induced peroxiredoxin oxidation, cytochrome c release, and caspase-3 activation. Catalase exhibited a strong inhibitory effect against the peroxiredoxin oxidation, and cytochrome c release induced by 6-OHDA; however, caspase-3 activation was not effectively inhibited by catalase. On the other hand, 6-OHDA-induced caspase-3 activation was inhibited in the presence of caspase-8, caspase-9, and calpain inhibitors. These results suggest that the H2O2 generated from 6-OHDA plays a pivotal role in 6-OHDA-induced peroxiredoxin oxidation, and cytochrome c release, while H2O2- and cytochrome c-independent caspase activation pathways are involved in 6-OHDA-induced neurotoxicity. These findings may contribute to explain the importance of generated H2O2 and secondary products as a second messenger of 6-OHDA-induced cell death signal linked to Parkinson's disease.

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

    Directory of Open Access Journals (Sweden)

    Chuyan Wu

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

  17. 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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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 ...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  3. A better mild traumatic brain injury model in the rat.

    Science.gov (United States)

    Takeuchi, Satoru; Nawashiro, Hiroshi; Sato, Shunichi; Kawauchi, Satoko; Nagatani, Kimihiro; Kobayashi, Hiroaki; Otani, Naoki; Osada, Hideo; Wada, Kojiro; Shima, Katsuji

    2013-01-01

    The primary pathology associated with mild -traumatic brain injury (TBI) is selective axonal injury, which may characterize the vast majority of blast-induced TBIs. Axonal injuries in cases of mild TBI have been considered to be the main factors responsible for the long-lasting memory or attentional impairment in affected subjects. Among these axonal injuries, recent attention has been focused on the cingulum bundle (CB). Furthermore, recent studies with diffusion tensor MR imaging have shown the presence of injuries of the CB in cases of mild TBI in humans. This study aimed to provide a better laboratory model of mild TBI.Sprague-Dawley rats were subjected to mild TBI using laser-induced shock waves (LISW) (sham, 0.5 J/cm(2), or 1.0 J/cm(2); n = 4 per group). Bodian-stained brain sections 14 days after LISW at 0.5 J/cm(2) or 1.0 J/cm(2) showed a decrease in the CB axonal density compared with the sham group, whereas there were no differences in the axonal density of the corpus callosum.The present study shows that this model is capable of reproducing the histological changes associated with mild TBI. PMID:23564112

  4. Cavo-portal transposition in rat: a new simple model

    Directory of Open Access Journals (Sweden)

    Andorno Enzo

    2007-08-01

    Full Text Available Abstract Background Liver transplantation in presence of diffuse portal vein thrombosis is possible by using caval blood as portal inflow, through cavo-portal transposition. However, clinical results are heterogeneous and experimental studies are needed, but similar hemodynamic conditions are difficult to obtain, especially in small animals. Herein we describe a new simple model of cavo-portal transposition in rat. Methods Spontaneous porto-systemic shunts are induced by subcutaneous transposition of the spleen. The presence of porto-caval shunts through the spleen permits the interruption of the main portal vein without splanchnic hemodynamic consequences. Cavo-portal transposition is achieved by anastomosing the inferior vena cava and the main portal vein after division of the pancreatic-duodenal vein. Results Selective angiography revealed total splanchnic blood diversion to the systemic venous circulation through the neoformed collaterals; macroscopical examination showed the absence of any signs of acute portal hypertension with normal liver and gut appearance. Conclusion This model of cavoportal transposition is simple, effective and it simulates the clinical hemodynamic condition since the porto-systemic shunts induced by splenic subcutaneous transposition correspond to the physiological inframesocolic collaterals during chronic portal thrombosis in man.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Defective copper binding to apo-ceruloplasmin in a rat model and patients with Wilson's disease.

    Science.gov (United States)

    Kojimahara, N; Nakabayashi, H; Shikata, T; Esumi, M

    1995-06-01

    To examine the mechanism of decrease in serum ceruloplasmin (Cp) in Long-Evans Cinnamon (LEC) rats, a proposed model of Wilson's disease, we analyzed Cp products at the stages of transcription and translation. Northern blot analysis and immunoblot analysis showed that the level and the molecular size of Cp mRNA and protein in LEC rats were similar to those in control Long-Evans-Agouti (LEA) rats. However, the ferroxidase activity of Cp was significantly decreased in LEC rats. We separated serum Cp into two forms by native polyacrylamide gel electrophoresis with pH modification: one was a holo-Cp with copper and ferroxidase activity, and the other was an inactive apo-Cp without copper. Holo-Cp was the predominant form in LEA rats and normal humans, whereas apo-Cp was the major form in LEC rats and patients with Wilson's disease. The cosegregation of apo-Cp predominance with the disease in LEC rats was analyzed using backcross rats. Apo-Cp was dominant in 8 of 11 offspring with disease but in none of 19 normal offspring. These results indicate that a genetic disturbance of copper binding to apo-Cp may be closely associated with the pathogenesis in LEC rats, and probably in Wilson's disease.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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)

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

    Science.gov (United States)

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

    2015-11-01

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

  10. Growth and the modeling/remodeling of the alveolar bone of the rat incisor.

    Science.gov (United States)

    Merzel, José; Salmon, Cristiane R

    2008-07-01

    The modeling and remodeling of the rat incisor alveolar bone was followed as the animals grew. The weight of the hemimandible, the length of the socket, and the width of the lower incisor were measured. Osteoclasts and resorption areas were identified by tartrate-resistant acid phosphatase staining. Fluorochrome markers were used to detect and measure osteogenic activities. In the socket related to the periodontal ligament, osteoclasts appeared in scattered sites as well as isolated sites of osteogenic activity, apparently without any variation related to the age of the animals. At the socket facing the dental follicle of young rats, the inner surface was lined with osteoclasts. The number of osteoclasts decreased steadily as the rats grew. In 1-year-old rats, in addition to a few scattered osteoclasts, the internal aspect of the labial wall showed some sites lined with osteoblasts and cement lines indicative of prior bone formation. In young rats, there was a continuous osteogenic activity at the external surface of this wall. The thickness of the labial wall of the socket remained apparently constant; therefore, bone resorption must have occurred at the internal side of the wall. Such osteogenic activity was not observed in old rats. The main forces acting on rat incisors, biting and eruption, are continuous through the life of the animals. Thus, these results indicate that the modeling of the alveolar bone related to the dental follicle, in young rats, can only be associated with another force, specifically, the growth of the incisor. PMID:18461598

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Effect of Electro—acupuncture on Rat Joint Pathomorphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    ZHANGYou-mei; HULing; 等

    2003-01-01

    Objective:To study the effect of electro-acupuncture(EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis.Methods:The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freunds adjuvant to the left hind sole.Forty Wistar rats were randomly divided into the model group,the low frequency(2Hz) EA group,the high frequency EA(100Hz)group and the body acupuncture group.After being modeled except the model group,the other three groups were treated with EA or body acupuncture in Yanglingquan points(bilater-al)for 3weeks,the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin,sectioning and staining with HE.Results:Obvious inflammatory cell infiltration,loosened synovial tissue,damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats.These pathologi-cal changes were significantly improved after treatment,and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group.Conclusion:High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant ar-thritis rat models.

  13. Effect of Electro-acupuncture on Rat Joint Patho-morphology of Chronic Adjuvant Arthritis Model

    Institute of Scientific and Technical Information of China (English)

    张幼美; 胡玲; 唐纯志; 曹伟

    2003-01-01

    Objective:To study the effect of electro-acupuncture (EA) on pathomorphological changes of joints in rat model of chronic adjuvant arthritis. Methods: The rat chronic adjuvant arthritis model was established by subcutaneous injection of 0.1 ml of complete Freund's adjuvant to the left hind sole. Forty Wistar rats were randomly divided into the model group, the low frequency (2 Hz) EA group, the high frequency EA (100 Hz) group and the body acupuncture group. After being modeled except the model group, the other three groups were treated with EA or body acupuncture in Yanglingquan points (bilateral) for 3 weeks, the left ankle joints and metatarsal joints of rats were taken for pathological examination by fixing with 10% formalin and embedding in paraffin, sectioning and staining with HE. Results: Obvious inflammatory cell infiltration, loosened synovial tissue, damage of articular cartilage and proliferation of synovial cells and granulation tissue were observed in the sections of joints in model rats. These pathological changes were significantly improved after treatment, and the effect in the high frequency EA group were significantly superior to that in the low frequency EA and body acupuncture group. Conclusion: High frequency EA could significantly improve the pathomorphological changes of joints in chronic adjuvant arthritis rat models.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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...

  17. Absence of "Warm-Up" during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling.

    Science.gov (United States)

    Myers, Catherine E; Smith, Ian M; Servatius, Richard J; Beck, Kevin D

    2014-01-01

    Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on "warm-up," transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the "standard" inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID:25183956

  18. Absence of warm-up during active avoidance learning in a rat model of anxiety vulnerability: Insights from computational modeling

    Directory of Open Access Journals (Sweden)

    Catherine E Myers

    2014-08-01

    Full Text Available Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of leverpress avoidance learning in Sprague-Dawley (SD rats, and in the inbred Wistar-Kyoto (WKY rat, which has been proposed as a model of anxiety vulnerability. We focus on warm-up, transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously-reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the standard inter-session interval is shortened from 48 to 24 hours, SD rats (but not WKY will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative, rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes.

  19. Exercise activates compensatory thermoregulatory reaction in rats: a modeling study.

    Science.gov (United States)

    Yoo, Yeonjoo; LaPradd, Michelle; Kline, Hannah; Zaretskaia, Maria V; Behrouzvaziri, Abolhassan; Rusyniak, Daniel E; Molkov, Yaroslav I; Zaretsky, Dmitry V

    2015-12-15

    The importance of exercise is increasingly emphasized for maintaining health. However, exercise itself can pose threats to health such as the development of exertional heat shock in warm environments. Therefore, it is important to understand how the thermoregulation system adjusts during exercise and how alterations of this can contribute to heat stroke. To explore this we measured the core body temperature of rats (Tc) running for 15 min on a treadmill at various speeds in two ambient temperatures (Ta = 25°C and 32°C). We assimilated the experimental data into a mathematical model that describes temperature changes in two compartments of the body, representing the muscles and the core. In our model the core body generates heat to maintain normal body temperature, and dissipates it into the environment. The muscles produce additional heat during exercise. According to the estimation of model parameters, at Ta = 25°C, the heat generation in the core was progressively reduced with the increase of the treadmill speed to compensate for a progressive increase in heat production by the muscles. This compensation was ineffective at Ta = 32°C, which resulted in an increased rate of heat accumulation with increasing speed, as opposed to the Ta = 25°C case. Interestingly, placing an animal on a treadmill increased heat production in the muscles even when the treadmill speed was zero. Quantitatively, this "ready-to-run" phenomenon accounted for over half of the heat generation in the muscles observed at maximal treadmill speed. We speculate that this anticipatory response utilizes stress-related circuitry.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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. ...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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 ...

  5. Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

    OpenAIRE

    Yang Cao; Meng-fei Zhuang; Ying Yang; Shu-wu Xie; Jin-gang Cui; Lin Cao; Ting-ting Zhang; Yan Zhu

    2014-01-01

    In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endom...

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

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

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

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

    Science.gov (United States)

    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

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

  10. Effect of Ethanol on Fluoroquinolone Efficacy in a Rat Model of Pneumococcal Pneumonia

    Science.gov (United States)

    Olsen, Keith M.; Gentry-Nielsen, Martha; Yue, Mei; Snitily, Mary U.; Preheim, Laurel C.

    2006-01-01

    This investigation compared the effect of ethanol on fluoroquinolone antibiotic efficacy and pharmacodynamics in an ethanol-fed rat model of pneumococcal pneumonia. Male Sprague-Dawley rats received a liquid diet containing 36% of total calories as ethanol. Paired controls (pair-fed controls) were fed a liquid diet without ethanol or received rat chow. Diets began 7 days before and continued for 10 days after transtracheal infections with 10 times the 50% lethal dose of type 3 Streptococcus pneumoniae. Beginning 18 h after infection, the rats received once daily subcutaneous phosphate-buffered saline, levofloxacin, moxifloxacin, or trovafloxacin at 50 or 100 mg/kg of body weight. White blood cell counts were determined, blood samples were collected for culture, and mortality was recorded. Additional rats were killed on day 5 for pharmacodynamic studies and quantitative cultures of bronchoalveolar lavage fluid. Bacteremia occurred by day 3 in 20 of 22 untreated rats. All 22 untreated rats died by day 9. Moxifloxacin treatment was effective in all diet groups at both the 50- and 100-mg/kg doses. In contrast, 50-mg/kg doses of levofloxacin and trovafloxacin improved survival in ethanol-fed rats but were ineffective in chow-fed rats. High-dose trovafloxacin at 100 mg/kg was associated with increased mortality in pair-fed rats. The free-fraction area under the concentration-time curve/MIC ratio exceeded 50 with all antibiotics in the ethanol group but dropped below 30 with levofloxacin and trovafloxacin in the pair- and chow-fed rats, with higher mortality. Achievement of adequate antibiotic-free fraction area under the concentration-time curve/MIC ratios helps overcome ethanol-induced immune defects induced in experimental pneumococcal pneumonia. PMID:16377688

  11. Rat as a model for direct pulp capping research

    OpenAIRE

    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 ...

  12. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    OpenAIRE

    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...

  13. Normal spatial and contextual learning for ketamine-treated rats in the pilocarpine epilepsy model.

    Science.gov (United States)

    McKay, B E; Persinger, M A

    2004-05-01

    Cognitive impairments frequently accompany epileptic disorders. Here, we examine two neuroprotective agents, the noncompetitive NMDA antagonist ketamine and the dopaminergic antagonist acepromazine, for their efficacy in attenuating cognitive impairments in the lithium-pilocarpine (LI-PILO) model of rat limbic epilepsy. Declarative-like cognitive behaviors were assessed in a Morris water maze task that consisted successively of spatial and nonspatial (cued platform) training. Whereas the ketamine-treated (Ket) LI-PILO rats performed equally in all respects to nonseized control rats for the spatial and nonspatial components of the water maze task, the acepromazine-treated (Ace) LI-PILO rats failed to demonstrate learning in either the hidden or cued platform variants of the task and did not demonstrate any place learning in the platform-removed probe trials. We further assessed nondeclarative (associative) cognitive behaviors with a standard contextual fear-conditioning protocol. LI-PILO rats treated with acepromazine failed to learn the Pavlovian relationship; Ket LI-PILO rats performed equivalently to nonseized controls. Cumulatively, these data suggest robust cognitive sparing for LI-PILO rats with pharmacological NMDA receptor antagonism following induction of status epilepticus (SE). This cognitive sparing occurs despite earlier findings that the mean amount of total brain damage with LI-PILO is equivalent for Ket and Ace rats.

  14. Quantitative MR application in depression model of rats: a preliminary study

    Institute of Scientific and Technical Information of China (English)

    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.

  15. Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

    Directory of Open Access Journals (Sweden)

    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.

  16. Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model

    Institute of Scientific and Technical Information of China (English)

    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.

  17. [Metabolic therapy of nephrolithiasis in two different rat models of kidney disease].

    Science.gov (United States)

    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

  18. The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model

    Science.gov (United States)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.

    2003-01-01

    Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.

  19. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    OpenAIRE

    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...

  20. Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    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

  1. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Eunice Molinar-Toribio

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

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

    Directory of Open Access Journals (Sweden)

    Osman Raif Karabacakb

    2014-10-01

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

  4. A Rat Model of Autologous Oral Mucosal Epithelial Transplantation for Corneal Limbal Stem Cell Failure

    Institute of Scientific and Technical Information of China (English)

    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).

  5. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Institute of Scientific and Technical Information of China (English)

    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.

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-10-01

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

  8. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  10. Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

    OpenAIRE

    Suzuki, Shugo; Naiki-Ito, Aya; KUNO, Toshiya; Punfa, Wanisa; Long, Ne; Kato, Hiroyuki; Inaguma, Shingo; Komiya, Masami; Shirai, Tomoyuki; TAKAHASHI,Satoru

    2014-01-01

    We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral pros...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  12. Objective validation of central sensitization in the rat UVB and heat rekindling model

    OpenAIRE

    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...

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

    Science.gov (United States)

    2016-01-01

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

  14. Normalization of ventral tegmental area structure following acupuncture in a rat model of heroin relapse

    Institute of Scientific and Technical Information of China (English)

    Rongjun Zhang; Xinghui Cai; Xiaoge Song; Chaoyang Dong; Xiaorong Hou; Lei Lv

    2014-01-01

    Drugs can cause obvious damage to the brain. To verify the relationship between acupuncture, neurotrophic factor expression and brain cell structural changes, this study established a rat model of heroin relapse using intramuscular injection of increasing amounts of heroin. During the detoxiifcation period, rat models received acupuncture at Baihui (DU20) and Dazhui (DU14). Electron microscopy demonstrated that the structure of the ventral tegmental area in heroin relapse rats gradually became normalized after acupuncture treatment. Immunohistochem-ical staining exhibited that the expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the ventral tegmental area following acupuncture. Moreover, the effects were similar to that of methadone, a type of medicine called an opioid. Results suggested that acupuncture at Baihui and Dazhui protected brain neurons against injury in rats with heroin relapse by promoting brain-derived neurotrophic factor and glial cell line-de-rived neurotrophic factor expression.

  15. Decreased accumulation of ultrasound contrast in the liver of nonalcoholic steatohepatitis rat model

    Institute of Scientific and Technical Information of China (English)

    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.

  16. Fractal analysis of alveolarization in hyperoxia-induced rat models of bronchopulmonary dysplasia.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Nana Takenaka-Ninagawa

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

  18. Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

    OpenAIRE

    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. ...

  19. Berberine Ameliorates Cold and Mechanical Allodynia in a Rat Model of Diabetic Neuropathy

    OpenAIRE

    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...

  20. Four-Point Bending as a Method for Quantitatively Evaluating Spinal Arthrodesis in a Rat Model

    OpenAIRE

    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...

  1. GASTROPROTECTIVE EFFECTS OF FRUITS OF TRIBULUS TERRESTRIS L. IN PYLORUS-LIGATED WISTAR RAT MODEL

    OpenAIRE

    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...

  2. Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

    OpenAIRE

    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...

  3. Effect of minimal enteral feeding on recovery in a methotrexate-induced gastrointestinal mucositis rat model

    OpenAIRE

    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...

  4. Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model

    OpenAIRE

    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...

  5. Lipopolysaccharide-Induced Biliary Factors Enhance Invasion of Salmonella enteritidis in a Rat Model

    OpenAIRE

    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...

  6. Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

    OpenAIRE

    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...

  7. Development and Characterization of a Novel Rat Model of Estrogen-Induced Mammary Cancer

    OpenAIRE

    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...

  8. Effects of Aloe vera leaf gel extract on rat peritonitis model

    OpenAIRE

    Ayca Altincik; Ferah Sönmez; Çigdem Yenisey; Soner Duman; Ayse Can; Nuriye Akev; Sevin Kirdar; Murat Sezak,

    2014-01-01

    Objectives: The aim of this study was to investigate the antibacterial, anti-inflammatory, and antioxidant activities and probable toxic effects of Aloe vera (AV) in a rat peritonitis model. Materials and Methods: Rats were divided into five groups: (1) Control group, (2) AV group, (3) peritonitis group (P), (4) peritonitis + AV group (P + AV), and (5) peritonitis + antibiotherapy group (P + Ab). Ultrafiltration (UF) rates were determined and colony and leukocyte counts were calculated in...

  9. The Effect of Ethanol Extracts of Vitex on Histomorphological Placenta in the Rat Model

    OpenAIRE

    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...

  10. Brinzolamide-induced retinopathy in neonatal rats: an alternative animal model of retinal neovascularization

    OpenAIRE

    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...

  11. Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

    OpenAIRE

    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 ...

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

    Directory of Open Access Journals (Sweden)

    Jorge V. Sotoca

    2014-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Igor Sukhotnik

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Thibaut Larcher

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

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

    Science.gov (United States)

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

    2014-01-01

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

  18. Changes of cerebral contents of neuropeptides in rat models of multiple ischemic dementia (MID)

    International Nuclear Information System (INIS)

    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)

  19. Effects of Exercise on Behavior and Peripheral Blood Lymphocyte Apoptosis in a Rat Model of Chronic Fatigue Syndrome

    Institute of Scientific and Technical Information of China (English)

    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...

  20. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

    Directory of Open Access Journals (Sweden)

    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.

  1. Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models

    Directory of Open Access Journals (Sweden)

    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.

  4. Fibrinogen and P-selectin expression in atherosclerosis model of Sprague Dawley rat

    Institute of Scientific and Technical Information of China (English)

    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.

  5. A physiologically based pharmacokinetic model for quinoxaline-2-carboxylic acid in rats, extrapolation to pigs.

    Science.gov (United States)

    Yang, X; Zhou, Y-F; Yu, Y; Zhao, D-H; Shi, W; Fang, B-H; Liu, Y-H

    2015-02-01

    A multi-compartment physiologically based pharmacokinetic (PBPK) model to describe the disposition of cyadox (CYX) and its metabolite quinoxaline-2-carboxylic acid (QCA) after a single oral administration was developed in rats (200 mg/kg b.w. of CYX). Considering interspecies differences in physiology and physiochemistry, the model efficiency was validated by pharmacokinetic data set in swine. The model included six compartments that were blood, muscle, liver, kidney, adipose, and a combined compartment for the rest of tissues. The model was parameterized using rat plasma and tissue concentration data that were generated from this study. Model simulations were achieved using a commercially available software program (ACSLXL ibero version 3.0.2.1). Results supported the validity of the model with simulated tissue concentrations within the range of the observations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, adipose, and muscles in rats were 0.98, 0.98, 0.98, 0.99, and 0.95, respectively. The rat model parameters were then extrapolated to pigs to estimate QCA disposition in tissues and validated by tissue concentration of QCA in swine. The correlation coefficients between the predicted and observed values were over 0.90. This model could provide a foundation for developing more reliable pig models once more data are available.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  7. Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats.

    Directory of Open Access Journals (Sweden)

    Marion Inostroza

    Full Text Available Affective symptoms such as anxiety and depression are frequently observed in patients with epilepsy. The mechanisms of comorbidity of epilepsy and affective disorders, however, remain unclear. Diverse models are traditionally used in epilepsy research, including the status epilepticus (SE model in rats, which are aimed at generating chronic epileptic animals; however, the implications of different SE models and rat strains in emotional behaviors has not been reported. To address this issue, we examined the emotional sequelae of two SE models of temporal lobe epilepsy (TLE--the lithium-pilocarpine (LIP model and the kainic acid (KA model--in two different rat strains (Wistar and Sprague-Dawley, which differ significantly in the pattern and extent of TLE-associated brain lesions. We found differences between LIP- and KA-treated animals in tests for depression-like and anxiety-like behaviors, as well as differences in plasma corticosterone levels. Whereas only LIP-treated rats displayed increased motivation to consume saccharin, both SE models led to reduced motivation for social contact, with LIP-treated animals being particularly affected. Evaluation of behavior in the open field test indicated very low levels of anxiety in LIP-treated rats and a mild decrease in KA-treated rats compared to controls. After exposure to a battery of behavioral tests, plasma corticosterone levels were increased only in LIP-treated animals. This hyperactivity in the hypothalamus-pituitary-adrenocortical (HPA axis was highly correlated with performance in the open field test and the social interaction test, suggesting that comorbidity of epilepsy and emotional behaviors might also be related to other factors such as HPA axis function. Our results indicate that altered emotional behaviors are not inherent to the epileptic condition in experimental TLE; instead, they likely reflect alterations in anxiety levels related to model-dependent dysregulation of the HPA axis.

  8. Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

    Directory of Open Access Journals (Sweden)

    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.

  9. Speech sound discrimination training improves auditory cortex responses in a rat model of autism

    Directory of Open Access Journals (Sweden)

    Crystal T Engineer

    2014-08-01

    Full Text Available Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes.

  10. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Directory of Open Access Journals (Sweden)

    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.

  11. Docosahexaenoic acid promotes dopaminergic differentiation in induced pluripotent stem cells and inhibits teratoma formation in rats with Parkinson-like pathology.

    Science.gov (United States)

    Chang, Yuh-Lih; Chen, Shih-Jen; Kao, Chung-Lan; Hung, Shih-Chieh; Ding, Dah-Ching; Yu, Cheng-Chia; Chen, Yi-Jen; Ku, Hung-Hai; Lin, Chin-Po; Lee, Kun-Hsiung; Chen, Yu-Chih; Wang, Jhi-Joung; Hsu, Chuan-Chih; Chen, Liang-Kung; Li, Hsin-Yang; Chiou, Shih-Hwa

    2012-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic (DA) neurons in the midbrain. Induced pluripotent stem (iPS) cells have shown potential for differentiation and may become a resource of functional neurons for the treatment of PD. However, teratoma formation is a major concern for transplantation-based therapies. This study examined whether functional neurons could be efficiently generated from iPS cells using a five-step induction procedure combined with docosahexaenoic acid (DHA) treatment. We demonstrated that DHA, a ligand for the RXR/Nurr1 heterodimer, significantly activated expression of the Nurr1 gene and the Nurr1-related pathway in iPS cells. DHA treatment facilitated iPS differentiation into tyrosine hydroxylase (TH)-positive neurons in vitro and in vivo and functionally increased dopamine release in transplanted grafts in PD-like animals. Furthermore, DHA dramatically upregulated the endogenous expression levels of neuroprotective genes (Bcl-2, Bcl-xl, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor) and protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis in iPS-derived neuronal precursor cells. DHA-treated iPS cells significantly improved the behavior of 6-hydroxydopamine (6-OHDA)-treated PD-like rats compared to control or eicosapentaenoic acid-treated group. Importantly, the in vivo experiment suggests that DHA induces the differentiation of functional dopaminergic precursors and improves the abnormal behavior of 6-OHDA-treated PD-like rats by 4 months after transplantation. Furthermore, we found that DHA treatment in iPS cell-grafted rats significantly downregulated the mRNA expression of embryonic stem cell-specific genes (Oct-4 and c-Myc) in the graft and effectively blocked teratoma formation. Importantly, 3 Tesla-magnetic resonance imaging and ex vivo green fluorescence protein imaging revealed that no teratomas were present

  12. Characterization of a new animal model of metabolic syndrome: the DahlS.Z-Lepr fa /Lepr fa rat

    OpenAIRE

    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,...

  13. Physiologically based biokinetic (PBBK) model for safrole bioactivation and detoxification in rats

    NARCIS (Netherlands)

    Martati, E.; Boersma, M.G.; Spenkelink, A.; Khadka, D.B.; Punt, A.; Vervoort, J.J.M.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    A physiologically based biokinetic (PBBK) model for alkenylbenzene safrole in rats was developed using in vitro metabolic parameters determined using relevant tissue fractions. The performance of the model was evaluated by comparison of the predicted levels of 1,2-dihydroxy-4-allylbenzene and 1'-hyd

  14. Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

    DEFF Research Database (Denmark)

    Gallon, L; Chandraker, A; Issazadeh-Navikas, Shohreh;

    1997-01-01

    Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown that...

  15. Genetic animal models for Absence epilepsy: a review of the WAG/Rij strain of rats

    NARCIS (Netherlands)

    Coenen, A.M.L.; Luijtelaar, E.L.J.M. van

    2003-01-01

    Based on the reviewed literature and the data presented in this paper, conclusions can be drawn with respect to the validity of the WAG/Rij strain of rats as a model for absence epilepsy in humans. The view that the WAG/Rij model has "face validity" is supported by the simultaneous presence of clini

  16. Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.

    Directory of Open Access Journals (Sweden)

    Amit Singhal

    Full Text Available BACKGROUND: Despite the availability of many animal models for tuberculosis (TB research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1 activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.

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

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-01-01

    Full Text Available Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage.

  18. Fused pulmonary lobes is a rat model of human Fraser syndrome

    International Nuclear Information System (INIS)

    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.

  19. Assessment of Alloxan-Induced Diabetic Rats as a Periodontal Disease Model Using a Selective Cyclooxygenase (COX)-2 Inhibitor

    OpenAIRE

    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 ...

  20. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

    OpenAIRE

    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...

  1. Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

    OpenAIRE

    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...

  2. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  3. Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2014-01-01

    Full Text Available In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

  4. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    Directory of Open Access Journals (Sweden)

    Caroline eMenard

    2014-05-01

    Full Text Available The LOU/C/Jall (LOU rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn, an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non obese aging

  5. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats.

    Science.gov (United States)

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-12-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than 30 brain regions. The measurements were performed using alpha-[(14)C]methyl-l-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental setup) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  6. A Comparative Study on Several Models of Experimental Renal Calcium Oxalate Stones Formation in Rats

    Institute of Scientific and Technical Information of China (English)

    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.

  7. A survival prediction model of rats in hemorrhagic shock using the random forest classifier.

    Science.gov (United States)

    Choi, Joon Yul; Kim, Sung Kean; Lee, Wan Hyung; Yoo, Tae Keun; Kim, Deok Won

    2012-01-01

    Hemorrhagic shock is the cause of one third of deaths resulting from injury in the world. Although many studies have tried to diagnose hemorrhagic shock early and accurately, such attempts were inconclusive due to compensatory mechanisms of humans. The objective of this study was to construct a survival prediction model of rats in hemorrhagic shock using a random forest (RF) model, which is a newly emerged classifier acknowledged for its performance. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), lactate concentration (LC), and perfusion (PF) measured in rats were used as input variables for the RF model and its performance was compared with that of a logistic regression (LR) model. Before constructing the models, we performed a 5-fold cross validation for RF variable selection and forward stepwise variable selection for the LR model to see which variables are important for the models. For the LR model, sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (ROC-AUC) were 1, 0.89, 0.94, and 0.98, respectively. For the RF models, sensitivity, specificity, accuracy, and AUC were 0.96, 1, 0.98, and 0.99, respectively. In conclusion, the RF model was superior to the LR model for survival prediction in the rat model.

  8. Antipsychotic-like effect of minocycline in a rat model

    OpenAIRE

    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...

  9. Triptolide ameliorates colonic fibrosis in an experimental rat model

    OpenAIRE

    Tao, Qingsong; Wang, Baochai; Zheng, Yu; Li, Guanwei; Ren, Jianan

    2015-01-01

    Triptolide is known to exert anti-inflammatory and immunomodulatory activities; however, its impact on intestinal fibrosis has not been previously examined. Based on our previous studies of the suppressive activity of triptolide on human colonic subepithelial myofibroblasts and the therapeutic efficacy of triptolide in Crohn’s disease, it was hypothesized that triptolide may have beneficial effects on intestinal fibrosis. In the present study, colonic fibrosis was induced in rats by 6 weekly ...

  10. [Study of pharmacokinetics of digoxin in ovariectomized rats model].

    Science.gov (United States)

    Jin, Yong-wen; Qin, Hong-yan; Rao, Zhi; Zhang, Guo-qiang; Ma, Yan Rong; Wei, Yu-Hui; Wu, Xin-an

    2015-12-01

    This study aims to investigate the change of plasma concentration of digoxin (DIG) in rats with ovariectomy. Twelve female SD rats were randomly assigned into ovariectomized group and sham group (n = 6). All rats plasma was collected after a single dose of 2 mg x kg(-1) DIG administrated orally, serum DIG concentration was determined by LC-MS/MS. The level of P-gp in the intestinal was analyzed by Western blotting. Pharmacokinetic calculations were performed on each individual using DAS 2.0 practical pharmacokinetic software. Compared with the sham group, C(max) of ovariectomized group decreased significantly (P < 0.01). There was no significant difference of AUC(0-t), and the level of P-gp was elevated in ovariectomized group. It was found that C(max) of DIG was significantly reduced after ovariectomy, and the change was associated with the decreased level of estrogen, which contributes to the increased level of P-gp. PMID:27169283

  11. General developmental health in the VPA-rat model of autism

    DEFF Research Database (Denmark)

    Favre, Mônica R; Rinaldi Barkat, Ta