Dataset Information

The effects of vasoactive intestinal peptide in the rat model of experimental autoimmune neuritis and the implications for treatment of acute inflammatory demyelinating polyradiculoneuropathy or Guillain-Barre syndrome.

ABSTRACT: Background:Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy that is characterized histologically by demyelination of peripheral nerves and nerve roots, infiltrates of T lymphocytes, and an inflammatory response that includes macrophage infiltrates. The aim of this study was to evaluate the effects of vasoactive intestinal peptide (VIP) in a rat model of experimental autoimmune neuritis (EAN). Methods:Forty male Lewis rats were divided into a control group (N=10), an EAN group (N=10), an EAN group treated with 15 nmol of VIP (N=10), and an EAN group treated with 30 nmol of VIP (N=10). The rat model was created by subcutaneous injection of P2 polypeptide (200 µg P257-81) into the base of the tail. Intraperitoneal injection of VIP was given on day 7. Rats were weighed and functionally evaluated using an EAN score (0-10). On day 16, the rats were euthanized. The sciatic nerve was examined histologically and using immunohistochemistry with antibodies against CD8, CD68, and forkhead box p3 (Foxp3). Serum concentrations of IL-17 and interferon-? (IFN-?) were measured by ELISA on day 16 after creating the EAN model. Results:The VIP-treated EAN groups had increased body weight and improved EAN scores compared with the untreated EAN group. CD8-positive and CD68-positive cells were significantly reduced in the EAN group treated with 30 nmol of VIP compared with 15 nmol of VIP. Foxp3-positive cells were significantly decreased in both EAN groups treated with VIP, and serum concentrations of IL-17 and IFN-? were significantly lower compared with the untreated EAN group (P<0.05). Conclusion:In a rat model of EAN, treatment with VIP resulted in functional improvement, reduced nerve inflammation, and decreased serum levels of inflammatory cytokines.

SUBMITTER: Jiao H

PROVIDER: S-EPMC6228051 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effects of vasoactive intestinal peptide in the rat model of experimental autoimmune neuritis and the implications for treatment of acute inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndrome.

Jiao Hong H Ren Huan H

Drug design, development and therapy 20181106

<h4>Background</h4>Guillain-Barré syndrome is an acute inflammatory demyelinating polyneuropathy that is characterized histologically by demyelination of peripheral nerves and nerve roots, infiltrates of T lymphocytes, and an inflammatory response that includes macrophage infiltrates. The aim of this study was to evaluate the effects of vasoactive intestinal peptide (VIP) in a rat model of experimental autoimmune neuritis (EAN).<h4>Methods</h4>Forty male Lewis rats were divided into a control gr ...[more]

PMID: 30464413

Similar Datasets

Project description:Background: Both Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are neurodegenerative and inflammatory demyelination disorders. Sporadic reports showed that the increased levels of thyroid function and autoantibodies are associated with GBS, CIDP, or both, but no systematic study has been reported. We assessed the differences of thyroid function and autoantibodies between GBS and CIDP in a Chinese cohort. Methods: A total of 256 patients were enrolled in this study. 175 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 81 patients hospitalized for diseases other than GBS or CIDP with mild symptoms were enrolled as a control group. Relevant clinical data, including thyroid function, and autoantibody examinations, were collected for statistical analysis. Results: In the comparison of thyroid function and autoantibody parameters, the levels of total thyroxine (TT4), thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab) in the GBS group were all higher than those in the CIDP and Control groups (P < 0.01). The thyroid antibody positive rates in the GBS and CIDP groups were 70.10 and 14.10%, respectively (P < 0.01). In the receiver operating characteristic (ROC) curve analysis, TT4, TPO-Ab, and TG-Ab were higher in the GBS group and lower in the CIDP group (P < 0.01). To achieve a high specificity of 97-99%, the diagnostic cutoff value of TPO-Ab was higher than 133 IU/mL (Sensitivity: 11.34%) or lower than 0.01 IU/mL (Sensitivity: 9.09%), while the diagnostic cutoff value of TG-Ab was higher than 261.1 IU/mL (Sensitivity: 2.06%) or lower than 0.46 IU/mL (Sensitivity: 11.69%). Multivariate logistic regression analysis showed that the differences in TPO-Ab were statistically significant between GBS patients with TPO-Ab was higher than 133 IU/mL and CIDP patients (P < 0.01); the differences in TG-Ab were statistically significant between GBS patients with TG-Ab was higher than 261.1 IU/mL and CIDP patients (P < 0.05). Conclusion: The elevation of thyroid autoantibodies was associated with GBS. TPO-Ab higher than 133 IU/mL or lower than 0.01 IU/mL and TG-Ab higher than 261.1 IU/mL or lower than 0.46 IU/mL had high specificity for differentiating between GBS and CIDP; therefore, TPO-Ab and TG-Ab can be used as biomarkers for the differential diagnosis of GBS and CIDP.

Project description:BackgroundGuillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are human autoimmune peripheral neuropathy. Besides humoral immunity, cellular immunity is also believed to contribute to these pathologies, especially CIDP. Sphingosine-1-phosphate receptor 1 (S1PR1) regulates the maturation, migration, and trafficking of lymphocytes. As of date, the therapeutic effect of sphingosine-1-phosphate receptor (S1PR) agonists on patients with GBS or CIDP remains unclear.MethodsTo evaluate the effect of siponimod, an agonist of S1PR1 and S1PR5, on experimental autoimmune neuritis (EAN), an animal model of autoimmune peripheral neuropathy, was used. Lewis rats were immunized with 125 μg of synthetic peptide from bovine P2 protein. Rats in the siponimod group were orally administered 1.0 mg/kg siponimod and those in the EAN group were administrated the vehicle on days 5-27 post-immunization (p.i.) daily. The symptom severity was recorded daily. The changes in the expression of cytokines and transcription factors in the lymph nodes and cauda equina (CE) which correlate with the pathogenesis of EAN and recovery of injured nerve were measured using reverse transcription quantitative PCR. Histological study of CE was also performed.ResultsFlaccid paralysis developed on day 11 p.i. in both groups. Siponimod relieved the symptom severity and decreased the expression of interferon-gamma and IL-10 mRNAs in lymph nodes and CE compared with that in the EAN group. The expression of Jun proto-oncogene (c-Jun) mRNA increased from the peak to the recovery phase and that of Sonic hedgehog signaling molecule (Shh) and Glial cell line-derived neurotrophic factor (Gdnf) increased prior to increase in c-Jun with no difference observed between the two groups. Histologically, siponimod also reduced demyelinating lesions and inflammatory cell invasion in CE.ConclusionsSiponimod has a potential to ameliorate EAN. Shh and Gdnf, as well as C-Jun played a significant role during the recovery of injured nerves.

Project description:Acute inflammatory demyelinating polyneuropathy (AIDP) - the main form of Guillain-Barre syndrome-is a rare and severe disorder of the peripheral nervous system with an unknown etiology. One of the hallmarks of the AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level. In this paper CSF peptidome and proteome in AIDP were analyzed and compared with multiple sclerosis and control patients. A total protein concentration increase was shown to be because of even changes in all proteins rather than some specific response, supporting the hypothesis of protein leakage from blood through the blood-nerve barrier. The elevated CSF protein level in AIDP was complemented by activization of protein degradation and much higher peptidome diversity. Because of the studies of the acute motor axonal form, Guillain-Barre syndrome as a whole is thought to be associated with autoimmune response against neurospecific molecules. Thus, in AIDP, autoantibodies against cell adhesion proteins localized at Ranvier's nodes were suggested as possible targets in AIDP. Indeed, AIDP CSF peptidome analysis revealed cell adhesion proteins degradation, however no reliable dependence on the corresponding autoantibodies levels was found. Proteome analysis revealed overrepresentation of Gene Ontology groups related to responses to bacteria and virus infections, which were earlier suggested as possible AIDP triggers. Immunoglobulin blood serum analysis against most common neuronal viruses did not reveal any specific pathogen; however, AIDP patients were more immunopositive in average and often had polyinfections. Cytokine analysis of both AIDP CSF and blood did not show a systemic adaptive immune response or general inflammation, whereas innate immunity cytokines were up-regulated. To supplement the widely-accepted though still unproven autoimmunity-based AIDP mechanism we propose a hypothesis of the primary peripheral nervous system damaging initiated as an innate immunity-associated local inflammation following neurotropic viruses egress, whereas the autoantibody production might be an optional complementary secondary process.

Dataset Information

The effects of vasoactive intestinal peptide in the rat model of experimental autoimmune neuritis and the implications for treatment of acute inflammatory demyelinating polyradiculoneuropathy or Guillain-Barre syndrome.

Publications

The effects of vasoactive intestinal peptide in the rat model of experimental autoimmune neuritis and the implications for treatment of acute inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets