Font Size: a A A

Effects Of Fibrin On Experimental Autoimmune Encephalolmyelitis And Value Of NMO-IgG On Neuromyelitis Optica

Posted on:2011-04-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y YangFull Text:PDF
GTID:1114360305959027Subject:Neurology
Abstract/Summary:PDF Full Text Request
Objective Multiple sclerosis (MS) was characterized with widespread inflammatory demyelination and axonal loss of central nervous system (CNS). Fibrinogen (fibrin) deposition was considered as one of the pathogenesis of MS. In the present study, we explored the capacity of prophylactic and therapeutic potential of fibrin depletion by batroxobin to affect the inflammatory demyelination process in experimental autoimmune encephalomyelitis (EAE) mice model.Methods In MOG-induced EAE, batroxobin was separately injected after disease inducement immediately (prevention) and after the appearance of clinical manifestations (suppression). At the time of postimmunization(p.i.) day 30,40,60, spinal cords and cerebellum tissue samples from EAE mice were collected for histopathologic and immunohistochemical methods. Molecular biological methods such as Western-blot and Real-time PCR were supplied to detect MBP, p-Akt, MHC-I and t-PA. Meantime, RAW264.7 cells were cultured for immunofluorescence to obseve the activation of macrophages irritated by fibrinogen after supplement of batroxobin. In addition, the latency and amplitude of P100 in flash VEP of batroxobin-treated mice and EAE control mice were observed.Results Our study found that prevention and suppression with batroxobin significantly ameliorated clinical severity of EAE, reduced inflammatory cells infiltration, demyelination and suppressed the activation of astrocytes and macrophages comprising the CD11b+population. The expressions of p-Akt were downregulated, while those of MBP were upregulated in prevention and suppression with batroxobin mice as compared to control mice. Moreover, our results showed that in vitro adding of batroxobin reversed the dendric-like formation of macrophages irritated by fibrinogen under inflammatory conditions. Furthermore, the latency was slightly prolonged and amplitude decreased of P100 in flash VEP of batroxobin-treated mice than those of EAE control mice.Conclusions In conclusion, fibrinogen depleting agent batroxobin has a benefical effect on EAE, therefore, strategy targeting fibrin as a potential therapy for EAE maybe helpful for the treatment of MS patients. Objective To investigate the value of AQP-4 antibody in diagnosis of neuromyelitis optica (NMO).Methods A total of 80 patients with NMO, high-risk NMO(HR-NMO),multiple sclerosis (MS), clinical isolated syndrome(CIS) and other neurological diseases (subacute combined degeneration, cerebral infarction, intracranial hemorrhage and neurofibroma) were included in the study. The titres of all patients' serum AQP-4 antibody were detected by indirect immunofluorence.Results There were significantly differences between patients with NMO, HR-NMO and MS, CIS, who experienced severe optical neuritis, transverse myelitis, brain normal in MRI scan, spinal-cord lesion more than 3 segments and serum AQP-4 antibody positive(p<0.05). The level of serum AQP-4 antibody of NMO, HR-NMO was higher than that of MS, while the level of serum AQP-4 antibody of MS was slightly higher than that of CIS and other diseases. The sensitivity and specificity of AQP-4 antibody were 82.6%,96.2%respectively in diagnosis of NMO.Conclusion AQP-4 antibody is valuable to diagnose NMO and differentiate from MS. Objective To investigate serum titres of AQP-4 antibody, levels of interferon-y (IFN-y) and interleukin-4 (IL-4) and their correlations in patients with neuromyelitis optica (NMO), multiple sclerosis (MS) and clinical isolated syndrome (CIS) in order to study the pathogenesis of NMO and MS.Methods A total of 130 patients with NMO including high-risk NMO (n=41), MS (n=59), CIS (n=15) and other neurological diseases (n=15) were included in the study. The titres of all patients'serum AQP-4 antibody were detected by indirect immunofluorence, and the levels of IFN-y and IL-4 were measured by ELISA kits.Results The titre of serum AQP-4 antibody in patients with NMO is much higher than those of patients with MS, CIS, and other diseases (p<0.05). However, there is also no significant difference of serum AQP-4 antibody among MS, CIS and other diseases(p>0.05). There is no significant difference of serum IFN-y and IL-4 among NMO, MS and other diseases(P>0.05). The titres of serum AQP-4 antibody in patients with NMO have positive correlation with IFN-y and IL-4 (r=0.36,0.35 respectively, p<0.05),on the other hand, the titres of serum AQP-4 antibody in patients with MS have not significant correlation with IFN-y and IL-4 (r=0.03,-0.10 respectively,p>0.05)。Conclusions AQP-4 antibody is not only valuable to differentiate NMO, MS and other diseases, but also may be have related to cytokines IFN-y and IL-4.
Keywords/Search Tags:multiple sclerosis, experimental autoimmune encephalomyeltis, fibrin, fibrinogen, batroxobin, Neuromyelitis optica, Multiple sclerosis, AQP-4 antibody, Multiple sclerosis, IFN-γ, IL-4
PDF Full Text Request
Related items