Zhen-Guo Liu

A population-based survey of multiple sclerosis in Shanghai, China.

Objective: To conduct a large population-based survey on multiple sclerosis (MS) prevalence in Shanghai, China. Methods: We established a network of physicians, mainly neurologists, for identifying prevalent patients with MS and systematically checked inpatient registers at each hospital in the study area for patients with a diagnosis of MS, neuromyelitis optica, or other demyelinating disorders. MS diagnosis in patients was validated by senior neurologists according to the McDonald criteria. Results: In total, 123 patients with a validated MS diagnosis from the study population, 8.86 million inhabitants with permanent residence in Shanghai, were alive on the prevalence day. The crude MS prevalence rate was 1.39 cases per 100,000 inhabitants (95% CI: 1.16 to 1.66 cases) in the study population in Shanghai. There were 79 female and 44 male patients with MS, a female-to-male ratio of 1.8. Nearly all (96%) of the patients with validated MS had been examined by MRI. Conclusion: Multiple sclerosis prevalence in Shanghai is in line with that reported for other Asian populations.

Clinical features of patients with multiple sclerosis from a survey in Shanghai, China

Objective To describe clinical features of patients with multiple sclerosis (MS) in Shanghai, China. Methods Prevalent patients with MS were identified and investigated by a network of physicians in 11 districts of Shanghai during the period from 1 September 2004 to 31 August 2005. Admission registries of each hospital in the study area were checked systematically for patients with a diagnosis of MS, neuromyelitis optica or other demyelinating disorders. All patients with collected information were evaluated by four senior neurologists according to the McDonald criteria. Results There were 249 (146 female and 103 male) patients with a confirmed MS diagnosis, at a female-to-male ratio of 1.4. The mean age at onset of MS was 37.4 years for the 249 patients with MS and, on the prevalence day, 42.7 years. The most frequent location of clinical MS lesions in the central nervous system was the spinal cord (61%), followed by the cerebrum (55%) and optic nerves (41%). Nearly all (96%) of the patients with MS had been examined by magnetic resonance imaging, and 226 (94%) patients of those examined were suggestive of MS. No family history of MS was found in any of the patients. Most (86%) of the patients had no or mild disability on the prevalence day (31 December 2004). Almost all (96%) patients with MS had been treated with corticosteroids. Conclusion Clinical features of patients with MS are described based on the information from the largest case series reported among Chinese. Comparisons and discussions are made with findings from the other populations.

Protective effects of intracerebral adenoviral-mediated GDNF gene transfer in a rat model of Parkinson's disease.

This study focuses on the potential protective effects of intracerebral adeno-viral mediated glial cell line derived neurotrophic factor (GDNF) gene transfer in a rat model of Parkinsons disease (PD). Thirty-five SD rats were divided into three groups to receive perinigral injections of recombinant adenovirus encoding GDNF (Ad-GDNF), LacZ (Ad-LacZ) or PBS, respectively. One week later, an intrastriatal injection of 6-hydroxydopamine (6-OHDA) was administered to induce the progressive degeneration of dopaminergic neurons. Immunohistochemistry showed that GDNF treatment prior to neuronal damage could promote survival and morphological recovery of tyrosine hydroxylase (TH)-positive neurons in the midbrain. Approximately 70% of nigral TH-positive cells survived in the Ad-GDNF group, compared to approximately 30% for the Ad-LacZ or PBS control group. Histochemical analysis of monoamine levels in the striatum demonstrated that the dopamine content was higher for the Ad-GDNF group than the control groups. Similarly, Ad-GDNF treated animals showed improved apomorphine-induced rotational behavior. The exogenous GDNF gene was efficiently expressed in the brain as detected by ELISA. This work demonstrates that intracerebral adeno-viral mediated GDNF gene transfer can protect dopaminergic neurons in vivo from 6-OHDA-induced injuries. The approach used in this study could potentially be used therapeutically in patients with PD and further work is required to explore this idea in depth.

Serum level of interleukin-6 in Chinese patients with multiple sclerosis

The aim of this study was to investigate the serum concentration of interleukin (IL)-6 in patients with relapsing-remitting MS (RR-MS), compare the difference between males and females, and explore the correlation between the serum concentration of IL-6 and clinical parameters like the current age, the age at onset, disease duration, disability (expanded disability status scale, EDSS), and the number of relapse. We compared the serum concentration of IL-6 in 39 patients with MS and 39 healthy controls matched with sex and age. The serum IL-6 concentration was measured by FlowCytomix. Compared to healthy controls, both the frequency of subjects with detectable level of IL-6 (P=0.005) and the serum concentration of IL-6 (P=0.004) were significantly higher in MS patients. When data were analyzed by gender, statistical significances between MS patients and healthy controls were observed only in females, although the frequency with detectable level and the serum concentration of IL-6 were higher in male MS patients than male controls. The serum level of IL-6 was found to be significantly positively correlated with the number of relapse for female MS patients (r(s)=0.511, P=0.009), with the current age for male MS patients (r(s)=0.700, P=0.005), and with the age at onset for all MS patients (r(s)=0.351, P=0.028). Our results may support that IL-6 is involved in the pathogenesis of MS and indicate that differences exist between male and female patients.

Long-term phenotypic correction of rodent hemiparkinsonism by gene therapy using genetically modified myoblasts.

Rat myoblasts were genetically modified to express tyrosine hydroxylase (TH) and produce dopamine in culture. Implanting TH gene-transfected myoblasts into the denervated striatum of 6-OHDA-lesioned rats significantly decreased rotational asymmetry by 50 to approximately 60%. Improvement persisted for up to 13 months. Genetically modified cells could survive and express transgene in the striatum as demonstrated by RT-PCR and immunohistochemical stain-ing. The dopamine content in the striatum tissue of the gene therapy group recovered to 49% of the normal level and was 25-fold higher than that of a control group receiving parental cells. Neither tumor formation nor immunorejection was observed in this study. These results show that myoblasts may be useful as gene carriers for ex vivo gene therapy in the CNS.

Chronic kidney disease is prevalent in Chinese patients admitted with verified cerebrovascular lesions and predicts short-term prognosis

OBJECTIVE Recent studies have identified chronic kidney disease (CKD) as an important risk factor for vasculopathies. While the link between CKD and cardiovascular events is well established, the link with cerebrovascular lesions (CVL) has been less well described. METHODS We studied the prevalence and prognostic importance of CKD in 1014 incident Chinese patients admitted with verified computerized tomography (CT) or magnetic resonance imaging (MRI) CVL (within the last 7 days). Laboratory data included the urinary microalbumin-to-creatinine ratio, routine urinalysis, fasting plasma glucose, serum creatinine, uric acid and other measures. Estimated glomerular filtration rate was calculated (using the modification of diet in renal disease formula) and CKD stages were classified according to kidney disease outcome quality initiative (K/DOQI) guidelines. Patients were followed for 30 days and any neurological sequelae were recorded. RESULTS A total of 1014 patients were enrolled (455 females, aged 68.56 ± 12.17 years). Among these, 708 had ischemic stroke, 197 hemorrhagic stroke and 109 had transient cerebral ischemic attack. Microalbuminuria was detected in 11.2% of patients, while 24.8% had proteinuria. Of all patients, 6.90% had Stage 1, 14.69% Stage 2, 21.60% Stage 3, 2.56% Stage 4 and 1.97% had Stage 5, giving a total prevalence of CKD at 47.7%. In logistic regression, proteinuria (odds ratio = 1.69), hyperglycemia (odds ratio = 1.67) and anemia (odds ratio = 1.37) were independent predictors for risk of sequelae at 30 days for both ischemic and non-ischemic CVL. CONCLUSION We report a high prevalence of CKD among Chinese patients with incident CVL. Proteinuria, hyperglycemia and anemia were prognostic factors in these patients.

The inhibition of CB 1 receptor accelerates the onset and development of EAE possibly by regulating microglia/macrophages polarization

Cannabinoid 1 receptor (CB1R) regulates the neuro-inflammatory and neurodegenerative damages of experimental autoimmune encephalomyelitis (EAE) and of multiple sclerosis (MS). The mechanism by which CB1R inhibition exerts inflammatory effects is still unclear. Here, we explored the cellular and molecular mechanisms of CB1R in the treatment of EAE by using a specific and selective CB1R antagonist SR141716A. Our study demonstrated that SR141716A accelerated the clinical onset and development of EAE, accompanied by body weight loss. SR141716A significantly up-regulated the expression of toll like receptor-4 (TLR-4) and nuclear factor-kappaB/p65 (NF-κB/p65) on microglia/macrophages of EAE mice as well as levels of inflammatory factors (TNF-α, IL-1β, IL-6) and chemokines (MCP-1, CX3CL1), accompanied by the shifts of cytokines from Th2 (IL-4, IL-10) to Th1 (IFN-γ)/Th17 (IL-17) in the spinal cords of EAE mice. Similar changes happened on splenic mononuclear cells (MNCs) except chemokine CX3CL1. Consistently, SR141716A promoted BV-2 microglia to release inflammatory factors (TNF-α, IL-1β, IL-6) while inhibited the production of IL-10 and chemokines (MCP-1, CX3CL1). Furthermore, when splenic CD4+ T cells co-cultured with SR141716A-administered BV-2 microglia, the levels of IL-4 and IL-10 were decreased while production of IL-17 and IFN-γ increased significantly. Our research indicated that inhibition of CB1R induced M1 phenotype-Th17 axis changed of microglia/macrophages through TLR-4 and NF-κB/p65 which accelerated the onset and development of EAE. Therefore, CB1R may be a promising target for the treatment of MS/EAE, but its complexity remains to be carefully considered and studied in further clinical application.