Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

纯系LEW鼠及裸小鼠膀胱灌注给药方式的探讨

 目的 探讨纯系LEW大鼠及裸小鼠膀胱灌注给药方法。方法 显微镜下解剖雌性LEW大鼠及裸小鼠尿道并根据解剖特征改造套管针。通过插入尿道的套管针膀胱灌注墨水，同时观察插管及膀胱充盈和染色情况。持续观察小鼠和大鼠生存状况及尿道损伤情况。结果 显微镜下可见雌性LEW大鼠及裸小鼠尿道与人存在明显差异。经尿道插管成功率高(100％)，动物生活状况没有明显受到插管灌注影响。结论 裸鼠膀胱灌注给药治疗是一种成功率高而可行的给药手段，动物膀胱灌注化疗模型可能为研究膀胱肿瘤治疗提供更为有效的工具。     

Immunosuppressive Effect of Cyclosporin A in Two Lymphocyte Transfer Models in Rats: Comparison of in Vivo and in Vitro Treatment

The immunosuppressive effect of CS-A was first studied in the assay for local GvHR. 3 x 10⁶ viable spleen cells from LEW rats were injected into one foot pad of LEW x BN hybrids and both PLN were weighed 7 days later. Treatment of the recipients with 3 doses of 50 mg/kg/day of CS-A suppressed this local GvHR. The effect was more pronounced when treatment started at the time of cell transfer rather than a few days before peak response. In-vitro incubation of the cellular inoculum with CS-A also prevented local GvHR. Histology of the PLN confirmed the quantitative results expressed by the PLN index. CS-A was further investigated in the EAE model in LEW rats. It protected rats sensitised with spinal cord emulsified in complete Freund's adjuvant for as long as they were treated with CS-A. Treatment delayed until after the appearance of EAE also markedly improved their condition. Oral treatment of recipients with 50 mg/kg/day CS-A prevented the development of adoptive EAE following the transfer of lymphoid cells conditioned in vitro. The presence of 0.1-1.0 μg CS-A in the medium of the sensitised lymphoid cells also inhibited the adoptive transfer of EAE. Finally, if the cells for the adoptive transfer were derived from CS-A-treated sensitised donors, they failed to induce EAE. Histological examination supported the symptomatic findings     

Aminoguanidine downregulates expression of cytokine-induced Fas and inducible nitric oxide synthase but not cytokine-enhanced surface antigens of rat islet cells

Autoimmune beta-cell destruction occurs directly by cell-mediated cytotoxicity or indirectly by cytokines released from infiltrating lymphocytes. Cytokines (IL-1beta/IFN-gamma) modify or induce expression of MHC antigens and ICAM-1 on beta-cells which can lead to an improved binding of T-lymphocytes to beta-cells and finally to an enhanced cell-mediated cytotoxicity. Cytokines also induce Fas-expression and inducible nitric oxide synthase (iNOS) causing generation of nitric oxide (NO) which is toxic for beta-cells. The iNOS inhibitor aminoguanidine (AG) delays diabetes onset, but does not reduce diabetes incidence. We wanted to know whether AG inhibits cytokine-induced expression of Fas, MHC antigens and ICAM-1 on beta-cells of LEW.1W and BB/OK rat islets after culture with IL-1beta/IFN-gamma. NO was completely inhibited by 5.0 mmol/L AG while 0.5 mmol/L had no inhibitory effect. AG downregulated Fas-expression on the surface of beta-cells. Cytokine-induced/enhanced expression of MHC class-II and ICAM-1 was not affected by any AG concentration. AG syngergistically increased cytokine-induced enhancement of MHC class-I antigen density. AG possibly blocks the indirect pathway of beta-cell damage in vivo due to inhibition of Fas and iNOS and improves direct cell-mediated cytotoxicity due to drastic increased MHC class-I expression. Inhibition of only one pathway of beta-cell destruction is not sufficient to prevent diabetes.     

Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression

We have shown that tacrolimus (TAC)-induced liver allograft acceptance is associated with migration and persistence of donor B cells and dendritic cells (DC). To clarify whether these MHC class II+ leukocytes have favorable roles in inducing tolerance, we analyzed recipient T cell reactions after allogeneic B or DC infusion. LEW rat B cells localized exclusively in BN host B cell follicles without any direct contact with host T cells. While few donor DC migrated to T cell areas and marginal zones, they were captured by host APC, suggesting that allogeneic MHC class II+ cells may induce immune reactions via the indirect pathway. Although DC-infused non-immunosuppressed recipients showed enhanced ex vivo anti-donor responses, persistent in vitro donor-specific hyporeactivity was seen equally with donor DC or B cell infusion under TAC. The results indicate that donor MHC class II+ APC are capable of regulating recipient immune reactions under TAC. Possible involvement of the indirect pathway of allorecognition is discussed.     

Spontaneous withdrawal in opiate-dependent Fischer 344, Lewis and Sprague-Dawley rats

The Lewis (LEW) and Fischer 344 (F344) inbred rat strains react differentially to acute morphine administration for a variety of behavioral and neurochemical measures. Investigations into effects of chronic morphine are less common, and investigations assessing dependence have been limited to those utilizing antagonist-precipitated withdrawal. The present experiment extended these assessments by examining spontaneous withdrawal in the LEW and F344 strains. In this preparation, males of the LEW, F344 and the outbred Sprague-Dawley (SD) strain were made dependent on morphine. Following this, opiate administration was terminated and animals were examined for spontaneous withdrawal by the acquisition of a withdrawal-associated taste aversion, changes in body weight loss and the display of several behaviors characteristic of opiate withdrawal. Although all morphine-treated subjects decreased body weight and avoided consumption of the withdrawal-associated solution, indicating successful induction of dependence, no difference between the strains emerged in these indices of withdrawal severity. The only strain difference to appear in the behavioral indicators of withdrawal was with diarrhea (LEW > F344). That the strains differ in acute reactivity to opioids, but not in the overall severity of withdrawal, was discussed in relation to the need to examine the relationship between neurochemical and behavioral data in a variety of neural systems and behavioral endpoints.     

40例低出生体重儿童社会适应行为智商水平对照研究

对40例低出生体重儿童采用儿童适应行为评定量表和韦氏儿童智力量表进行测试,发现该组儿童适应行为评定得分随年龄增长而增加,但发展水平普遍低于对照组。提示应重视和加强对此类儿童特殊的早期教育和训练,并为其有针对性地进行早期教育和训练提供科学依据。     

Prevention of spontaneous immune-mediated diabetes development in the LEW.1AR1-iddm rat by selective CD8+ T cell transfer is associated with a cytokine shift in the pancreas-draining lymph nodes

Aims/hypothesis  The LEW.1AR1-iddm rat is an animal model of spontaneous type 1 diabetes mellitus. This study analysed how adoptive transfer of selective T cell subpopulations affects the incidence of diabetes. Methods  CD4⁺ or CD8⁺ T cells were isolated from diabetic LEW.1AR1-iddm rats or diabetes-resistant LEW.1AR1 rats. Cells were selectively transferred into athymic LEW.1AR1-Whn ^rnu or prediabetic LEW.1AR1-iddm rats. The animals were monitored for blood glucose, islet infiltration and immune cell composition of pancreas-draining lymph nodes. Results  After adoptive transfer of CD4⁺ T cells from diabetic LEW.1AR1-iddm rats into athymic LEW.1AR1-Whn ^rnu rats, 50% of the recipients developed diabetes. Transfer of CD8⁺ T cells failed to induce diabetes. Only 10% of the athymic recipients became diabetic after co-transfer of CD4⁺ and CD8⁺ T cells. Adoptive transfer of CD8⁺ T cells from LEW.1AR1 or diabetic LEW.1AR1-iddm rats into prediabetic LEW.1AR1-iddm rats significantly reduced the incidence of diabetes. In protected normoglycaemic animals regulatory CD8⁺/CD25⁺ and CD4⁺/CD25⁺ T cell subpopulations that were also FOXP3-positive accumulated in the pancreas-draining lymph nodes. In this lymphatic organ, gene expression of anti-inflammatory cytokines was significantly higher than in diabetic rats. Conclusions/interpretation  Our results show that adoptive transfer of CD4⁺ but not CD8⁺ T cells from diabetic LEW.1AR1-iddm rats induced diabetes development. Importantly, CD8⁺ T cells from diabetic LEW.1AR1-iddm rats and diabetes-resistant LEW.1AR1 rats provided protection against beta cell destruction. The accumulation of regulatory T cells in the pancreas-draining lymph nodes from protected rats indicates that transferred CD8⁺ T cells may have beneficial effects in the control of beta cell autoimmunity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. T. Arndt and D. Wedekind contributed equally to this study.     

Effects of stress modulation on morphine-induced conditioned place preferences and plasma corticosterone levels in Fischer, Lewis, and Sprague–Dawley rat strains

Rationale There is a direct relationship between hypothalamic–pituitary–adrenal axis (HPA) reactivity and susceptibility to drug use in outbred rats. Specifically, manipulations that increase or decrease HPA activity also increase or decrease drug intake, respectively. Interestingly, this relationship has not been established in the inbred Fischer (F344) and Lewis (LEW) rat strains that are often used as animal models of susceptibility to drug use.Objective The present study investigated the effects of manipulations known to affect HPA activity on morphine-induced conditioned place preference (CPP) in male LEW, F344, and Sprague–Dawley (SD) rats.Materials and methods In experiment 1, animals were exposed to an injection of methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) and 2-h restraint stress prior to the conditioning of a morphine-induced place preference (1, 4, or 10 mg/kg subcutaneous). In experiment 2, animals were chronically exposed to corticotropin-releasing hormone type 1 receptor antagonist, antalarmin, prior to CPP training. The effects of DMCM/restraint and antalarmin on corticosterone levels were examined in experiments 3 and 4.Results In outbred rats, DMCM/restraint increased both HPA activity and morphine-induced CPP, while antalarmin decreased CPP and produced a slight, but nonsignificant, decrease in corticosterone levels. In the inbred rats, however, DMCM/restraint increased plasma corticosterone yet decreased place preferences in the LEW strain, and antalarmin treatment decreased plasma corticosterone but increased place preferences in the F344 strain.Conclusions These data suggest that the relationship between stress and drug use may be nonmonotonic. The use of these inbred strains in genetic analysis of drug addiction may require reexamination.