Rabbit Model Of Antigen-induced Arthritis Research Articles

Value of contrast-enhanced ultrasound for detection of synovial vascularity in experimental rheumatoid arthritis: an exploratory study.

ObjectiveThis study aimed to examine the associations between contrast-enhanced ultrasound (CEUS) imaging and synovial hypervascularity and synovitis score in a rabbit model of antigen-induced arthritis (AIA), compared with power Doppler ultrasound (PDUS).MethodsWe investigated 50 knee joints in 25 AIA rabbits (AIA group), and 10 knee joints in five sham-injected rabbits (control group). PDUS and CEUS images were evaluated at the 8th week. Ultrasound-guided synovial biopsies were targeted in the area with hypervascularity, and synovial microvessel density (MVD) was evaluated by immunohistochemical staining of CD31.ResultsThe PDUS score was significantly higher in the AIA group (2.61 ± 0.78) compared with the control group (0.50 ± 0.53). CEUS in the AIA group revealed a fast-in/slow-out pattern of contrast enhancement. MVD revealed by CD31+ vessel count and the synovitis score were significantly higher in the AIA group compared with the control group. In the AIA group, CEUS findings showed a better correlation with MVD revealed by CD31+ and synovitis score than PDUS findings.ConclusionCEUS is superior to PDUS for estimating synovial hypervascularity and hyperplasia in experimental rheumatoid arthritis.

Correlative BOLD MR imaging of stages of synovitis in a rabbit model of antigen-induced arthritis

Because of the ability of blood-oxygen-level-dependent (BOLD) MRI to assess blood oxygenation changes within the microvasculature, this technique holds potential for evaluating early perisynovial changes in inflammatory arthritis. To evaluate the feasibility of BOLD MRI to detect interval perisynovial changes in knees of rabbits with inflammatory arthritis. Rabbit knees were injected with albumin (n=9) or saline (n=6) intra-articularly, or were not injected (control knees, n=9). Except for two rabbits (albumin-injected, n=2 knees; saline-injected, n=2 knees) that unexpectedly died on days 7 and 21 of the experiment, respectively, all other animals were scanned with BOLD MRI on days 0, 1, 7, 14, 21 and 28 after induction of arthritis. T2*-weighted gradient-echo MRI was performed during alternate 30 s of normoxia/hyperoxia. BOLD MRI measurements were compared with clinical, laboratory and histological markers. Percentage of activated voxels was significantly greater in albumin-injected knees than in contralateral saline-injected knees (P=0.04). For albumin-injected knees (P<0.05) and among different categories of knees (P=0.009), the percentage of activated BOLD voxels varied over time. A quadratic curve for on-and-off BOLD difference was delineated for albumin- and saline-injected knees over time (albumin-injected, P=0.047; saline-injected, P=0.009). A trend toward a significant difference in synovial histological scores between albumin-injected and saline-injected knees was noted only for acute scores (P=0.07). As a proof of concept, BOLD MRI can depict perisynovial changes during progression of experimental arthritis.

Liposome‐bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis

We previously observed that T lymphocytes present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) were sensitive to APO2L/TRAIL. In addition, there was a drastic decrease in the amount of bioactive APO2L/TRAIL associated with exosomes in SF from RA patients. This study was undertaken to evaluate the effectiveness of bioactive APO2L/TRAIL conjugated with artificial lipid vesicles resembling natural exosomes as a treatment in a rabbit model of antigen-induced arthritis (AIA). We used a novel Ni(2+)-(N-5-amino-1-carboxypentyl)-iminodiacetic acid)-containing liposomal system. APO2L/TRAIL bound to liposomes was intraarticularly injected into the knees of animals with AIA. One week after treatment, rabbits were killed, and arthritic synovial tissue was analyzed. Tethering APO2L/TRAIL to the liposome membrane increased its bioactivity and resulted in more effective treatment of AIA compared with soluble, unconjugated APO2L/TRAIL, with substantially reduced synovial hyperplasia and inflammation in rabbit knee joints. The results of biophysical studies suggested that the increased bioactivity of APO2L/TRAIL associated with liposomes was due to the increase in the local concentration of the recombinant protein, augmenting its receptor crosslinking potential, and not to conformational changes in the protein. In spite of this increase in bioactivity, the treatment lacked systemic toxicity and was not hepatotoxic. Our findings indicate that binding APO2L/TRAIL to the liposome membrane increases its bioactivity and results in effective treatment of AIA.

Establishment of a Experimental Antigen-induced Arthritis in Rabbit and Evaluation of its MRT Manifestations

Objective To establish a experimental rabbit model of antigen-induced arthritis and discuss its MRI manifestations.Methods Unilateral arthritis was induced by means of intraartieular injection of ovalbumin in 7 knees of 7 rabbits that had been presensitized to the same antigen.All knees were imaged at 5,15 days after onset of arthritis.MR findings were correlated with histopathologic findings.Results 6 knees with intraarticular injection of antigen suspension developed unilateral arthritis.Precontrast image showed thickening of joint effusion and synovium.The Joint effusion or synovium showed hypo-or/so-intensity on T1-weighted spin-echo,while inhomogeneouos hyper-intensity on T2-weighted spin-echo.It could be difficult to differentiated from one another.Postcontrast image (after Gd-DTPA administration) showed marked enhancement,whereas joint effusion did not.Synovium increasing was more distinctive on 15 day than on 5 day after intraarticular injection.The results of histopathologic evaluation confirmed the MR findings,with presence of marked to extensive synovial hyperplasia in all 6 arthritic knees of the antigen-injected group.Cellular infiltrates containing monocytes,lymphocytes,and macrophages were noted within the hyperplastic synovium of the arthritic knees.Conclusions The pathological process development and MRI manifestations in the rabbit model of antigen-induced arthritis is similar to that in human beings,so that it is a good lab model of rheumatoid arthritis. Key words: Experimental; Rabbit model of antigen-induced arthritis; MRI

Ultrasmall superparamagnetic iron oxide-enhanced MRI in a rabbit model of antigen-induced arthritis: a preliminary study

目的 探索超微超顺磁性氧化铁粒子(USPIO)增强MRI监测兔抗原诱导性膝关节炎的可行性及理想成像序列.方法 9只雌性新西兰大白兔,后腿右膝关节(简称右膝关节)腔注入甲基化小牛血清蛋白(mBSA)0.5 ml(2 mg/ml)诱导关节炎模型,后腿左膝关节(简称左膝关节)作为对照.另选3只制成假模型组.模型成功后9～28 d(平均21.3 d)经静脉注入USPIO(0.3 ml/kg),分别于增强前、增强后24 h行MRI扫描,其中2只于48、72 h再行MRI扫描.扫描方案包括T1WI、FSET2WI、短时反转恢复(STIR)序列及梯度回波(GRE)T2*WI.测量USPIO增强前后滑膜的信噪比(SNR)及SNR变化(△SNR),行配对t检验,并与病理结果相对照.结果 9只大白兔右膝均成功诱导关节炎模型,病理显示滑膜增生,血管翳形成,有大量吞噬USPIO的滑膜巨噬细胞浸润;MRI示滑膜增厚,厚度为(2.07±0.97)mm;关节囊积液.注射USPIO后24 h,T1WI信号升高[△SNR为(41.91±27.94)%],T2WI和T2*WI信号下降[△SNR分别为(-34.92±11.77)%和(-57.24±16.05)%],各序列增强前后SNR差异有统计学意义(P＜0.05).注射后48 h,信号强度开始恢复,72 h信号基本同增强前.模型组左膝关节及假模型组双膝关节滑膜正常,关节囊无明显积液.结论 滑膜巨噬细胞吞噬氧化铁粒子是引起USPIO增强MRI信号改变的基础,GRE序列是反映USPIO增强效应的敏感序列。

Evaluation of indium-111 chloride as a radiopharmaceutical for joint imaging in a rabbit model of arthritis.

The potential use of 111In-chloride as a radiopharmaceutical for quantitating the extent of synovitis was investigated in a rabbit model of antigen-induced arthritis. Rabbits with monoarticular disease were injected with 111In-chloride and imaged at 30 minutes and 24, 48, 72, and 96 hours. In control knee joints, the ratio of activity in the knee to a soft-tissue region in the thigh remained constant (1.5-1.85:1); in arthritic knees, the 111In uptake ratio increased from 2:1 to 3.2, 3.5, 3.9, and 4.6:1 at the later time points. The difference between the knee-to-soft-tissue ratios observed in the control and involved joints was significant (P less than .01, 48-96 hr). Tissue distribution measurements demonstrated that the synovium and intra-articular structures covered by synovium in arthritic joints had the highest concentration of 111In. In control joints, these tissues were found to take up tenfold less activity. Good correlation was observed between the 111In knee-to-soft-tissue ratios calculated from the images and histologic assessment of the severity of synovitis.