Germinomas of the basal ganglia and thalamus: Four case reports.

BACKGROUND: The early diagnosis of basal ganglia and thalamus germinomas is often difficult due to the absence of elevated tumor markers, and atypical clinical symptoms and neuroimaging features. CASE SUMMARY: Four male children aged 8 to 15 years were diagnosed with germinomas in the basal ganglia and thalamus by stereotactic biopsy from 2017 to 2019. All patients developed hemiplegia except patient 4 who also had cognitive decline, speech disturbance, nocturnal enuresis, polydipsia, polyuria, precocious puberty and abnormalities of thermoregulation. All four cases were alpha-fetoprotein and beta-human chorionic gonadotrophin (ß-HCG) negative except patient 3 who had slightly elevated ß-HCG in cerebrospinal fluid (CSF). No malignant cells were detected in the patients' CSF. Brain magnetic resonance imaging findings were diverse in these patients with the exception of the unique and common characteristics of ipsilateral hemisphere atrophy, especially in the cerebral peduncle. All patients were diagnosed with germinomas of the basal ganglia and thalamus by stereotactic brain biopsy. CONCLUSION: Stereotactic brain biopsy is necessary to confirm the diagnosis of ectopic germinomas. Serial neuroimaging studies can not only differentiate disease but also determine the biopsy site.

Update of inflammasome activation in microglia/macrophage in aging and aging-related disease.

Aging and aging-related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging-related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence "inflammaging" and aging-related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging-related diseases are also discussed.

Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of gastrointestinal tract in the world, and the long-term prognosis for ESCC patients still remains dismal due to the lack of effective early diagnosis biomarkers. MATERIALS AND METHODS: Western blot and immunochemistry were used to determine the expression of PRR11 in 201 clinicopathologically characterized ESCC specimens. The effects of PRR11 on stem cell-like traits and tumorigenicity were examined by tumor sphere formation assay and SP assays in vitro and by a tumorigenesis model in vivo. The mechanism by which PRR11 mediated Wnt/ß-catenin signaling was explored using luciferase reporter, immuno-chemistry, and real time-PCR (RT-PCR) assays. RESULTS: We found that PRR11 was markedly upregulated, at the level of both transcription and translation, in ESCC cell lines as compared with normal esophageal epithelial cells (NECCs). Immunohistochemical analysis showed that 69.2% paraffin-embedded archival ESCC specimens exhibited high levels of PRR11 expression, and multivariate analysis revealed that PRR11 upregulation might be an independent prognostic indicator for the survival of patients with ESCC. Furthermore, overexpression of PRR11 dramatically enhanced, whereas inhibition of PRR11 reduced the capability of cancer stem cell (CSC)-like phenotypes and tumorigenicity of ESCC cells both in vitro and in vivo. Mechanically, we demonstrated PRR11-enhanced tumorigenicity of ESCC cells via activating Wnt/ß-catenin signaling, and PRR11 expression is found to be significantly correlated with ß-catenin nuclear location in ESCC. CONCLUSION: Our findings suggest that the PRR11 might represent a novel and valuable prognostic marker for ESCC progression and play a role during the development and progression of this malignancy.

TRIM31 promotes glioma proliferation and invasion through activating NF-κB pathway.

BACKGROUND: Glioma is the most lethal primary brain tumor, the survival rate still isn't improved in the past decades. It's essential to study the regulatory mechanism of glioma progression, hoping to find new therapy targets or methods. The family of tripartite motif (TRIM) containing proteins are E3 ubiquitination ligases, which play critical role in various tumor progression. METHODS: Cell proliferation and invasion were analyzed by colony formation assay, soft agar growth assay, BrdU incorporation assay and transwell invasion assay. Luciferase reporter analysis was used to analyze NF-κB pathway activity. RESULTS: We found TRIM31 was upregulated in glioma cells and tissues, its overexpression significantly promoted glioma cell proliferation and invasion, while its knockdown significantly inhibited glioma cell proliferation and invasion. Mechanism analysis found TRIM31 promoted NF-κB pathway activity and increased its targets expression. NF-κB inhibition reversed the phenotype caused by TRIM31, confirming TRIM31 promoted glioma progression through activating NF-κB pathway. Using clinical specimens found TRIM31 expression was positively correlative with NF-κB activity. CONCLUSION: This study found TRIM31 promoted glioma proliferation and invasion through activating NF-κB activity.

Correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease: A case-control study.

This research was aimed to explore correlation of gene polymorphisms of CD36 and ApoE with susceptibility of Alzheimer disease (AD).This study was a case-control study. Two hundred eleven AD hospitalized patients were selected as the AD group and 241 subjects were selected as the control group. PCR-RFLP was used to detect three loci (rs7755, rs3211956, and rs10499859) of CD36 gene and ApoE genotype. Chi-square test and univariate nonconditional logistic regression analysis were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI). The haplotypes were constructed using SHEsis online software and the correlation between haplotypes and AD was analyzed. Meanwhile, differences of 3 alleles of ApoE and 6 genotypes (E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, E4/E4) were compared between AD and control groups.The frequencies of rs7755 genotype (χ = 10.780, P = .005) and allele (χ = 10.549, P = .001) were statistically different between 2 groups. The genotype frequency of rs3211956 was statistically different between AD and control groups (χ = 10.119, P = .006). For the rs7755 locus, GG genotype (OR: 2.013, 95% CI: 1.098-3.699) was an independent risk factor for AD compared with AA genotype. In the dominant model, the risk to develop AD in AG/GG genotype was 1.686 times higher than AA genotype. For the rs3211956 locus, compared with TT genotype, GT genotype (OR: 0.536, 95% CI: 0.340-0.846) was a protective factor for AD after adjusting various physiological and biochemical factors. In the dominant model, the risk of GT/GG genotype to develop AD was reduced by 41.6%. For ApoE gene, the distribution differences of E2/E3 (χ = 9.216, P = .002), E3/E4 (χ = 7.728, P = .005), and E4/E4 had statistical significance between the 2 groups. The frequencies of allele E2 (χ = 9.359, P = .002) and E4 (χ = 13.995, P < .001) were statistically significant between AD and control groups.The rs7755 and rs3211956 loci polymorphisms of CD36 gene and genotype E2/E3, E3/E4, E4/E4 of ApoE gene, and E2 and E4 alleles were statistically related with AD.

An adolescence-onset male leukoencephalopathy with remarkable cerebellar atrophy and novel compound heterozygous AARS2 gene mutations: a case report.

Mutations in the mitochondrial alanyl-transfer (t)RNA synthetase 2 (AARS2; OMIM 612035) have been linked to leukoencephalopathy recently. Until now, there have been only 13 cases reported in the literature. Hence, the clinical and genetic characteristics of this disease are not fully understood. Here, we reported an adolescence-onset male leukoencephalopathy patient characterized by progressive limb tremor at the age of 17 years. He had no signs of a cardiomyopathy. Magnetic resonance imaging scanning demonstrated severe cerebellar atrophy and white matter abnormalities involving descending tracts. Focused exome sequencing revealed he had novel compound heterozygous mutations in AARS2 gene (c.2265dupA; p.Arg756fs and c.650C>T; p.Pro217Leu). The patient was diagnosed with AARS2 mutation-related leukodystrophy (AARS2-L). We report a case with novel AARS2 gene mutations with developed striking cerebellar atrophy and leukoencephalopathy, which helps to further understand the clinical and genetic heterogeneity of AARS2-L.

Wnt5a Promotes Cortical Neuron Survival by Inhibiting Cell-Cycle Activation.

ß-Amyloid protein (Aß) is thought to cause neuronal loss in Alzheimer's disease (AD). Aß treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aß42 promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aß42 treated cortical neurons. Furthermore, Wnt5a signals through the non-canonical Wnt/Ca2+ pathway to suppress cyclin D1 expression and negatively regulate neuronal cell-cycle activation in a cell-autonomous manner. Together, aberrant downregulation of Wnt5a signaling is a crucial step during Aß42 induced cortical neuron apoptosis and might contribute to AD-related neurodegeneration.

Neutralization of Interleukin-9 Decreasing Mast Cells Infiltration in Experimental Autoimmune Encephalomyelitis.

BACKGROUND: Th9 cells are a newly discovered CD4+ T helper cell subtype, characterized by high interleukin (IL)-9 secretion. Growing evidences suggest that Th9 cells are involved in the pathogenic mechanism of multiple sclerosis (MS). Mast cells are multifunctional innate immune cells, which are perhaps best known for their role as dominant effector cells in allergies and asthma. Several lines of evidence point to an important role for mast cells in MS and its animal models. Simultaneously, there is dynamic "cross-talk" between Th9 and mast cells. The aim of the present study was to examine the IL-9-mast cell axis in experimental autoimmune encephalomyelitis (EAE) and determine its interaction after neutralizing anti-IL-9 antibody treatment. METHODS: Female C57BL/6 mice were randomly divided into three groups (n = 5 in each group): mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE (EAE group), EAE mice treated with anti-IL-9 antibody (anti-IL-9 Abs group), and EAE mice treated with IgG isotype control (IgG group). EAE clinical score was evaluated. Mast cells from central nervous system (CNS) were detected by flow cytometry. The production of chemokine recruiting mast cells in the CNS was explored by reverse transcription-polymerase chain reaction (RT-PCR). In mice with MOG-induced EAE, the expression of IL-9 receptor (IL-9R) complexes in CNS and spleen mast cells was also explored by RT-PCR, and then was repeating validated by immunocytochemistry. In vitro, spleen cells from EAE mice were cultured with anti-IL-9 antibody, and quantity of mast cells was counted by flow cytometry after co-culture. RESULTS: Compared with IgG group, IL-9 blockade delayed clinical disease onset and ameliorated EAE severity (t = -2.217, P = 0.031), accompany with mast cells infiltration decreases (day 5: t = -8.005, P < 0.001; day 15: t = -11.857, P < 0.001; day 20: t = -5.243, P = 0.001) in anti-IL-9 Abs group. The messenger RNA expressions of C-C motif chemokine ligand 5 (t = -5.932, P = 0.003) and vascular cell adhesion molecule-1 (t = -4.029, P = 0.004) were significantly decreased after IL-9 neutralization in anti-IL-9 Abs group, compared with IgG group. In MOG-induced EAE, the IL-9R complexes were expressed in CNS and spleen mast cells. In vitro, splenocytes cultured with anti-IL-9 antibody showed significantly lower levels of mast cells in a dose-dependent manner, compared with splenocytes cultured with anti-mouse IgG (5 µg/ml: t = -0.894, P = 0.397; 10 µg/ml: t = -3.348, P = 0.019; 20 µg/ml: t = -7.639, P < 0.001). CONCLUSIONS: This study revealed that IL-9 neutralization reduced mast cell infiltration in CNS and ameliorated EAE, which might be relate to the interaction between IL-9 and mast cells.

Baicalein improves behavioral dysfunction induced by Alzheimer's disease in rats.

BACKGROUND: Alzheimer's disease (AD) is considered to be a neurodegenerative disorder that is characterized by increased oxidative stress. Medicinal plants, with their antioxidant properties, have been used to cure several human diseases. The aim of the current study was to explore the protective and therapeutic effect of baicalein on AD-induced rats. MATERIALS AND METHODS: Swiss Wistar rats were used in the study. The rats were divided into five groups. Group I: normal control group treated with water; Group II: disease control treated with AlCl3 to induce the mimicking AD for 4 successive weeks (SW); Group III: normal control group treated with baicalein (5 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group IV: normal control group treated with baicalein (10 mg/kg) for 2 SW followed by combination of baicalein and AlCl3 for 4 SW; Group V: normal control group treated with rivastigmine (0.3 mg/kg) for 2 SW followed by combination of rivastigmine and AlCl3 for 4 SW. Moreover, the therapeutic groups are as follows: Group VI: AD disease control treated with AlCl3 for 4 SW and serving as the therapeutic positive group; Group VII: AD disease control + baicalein (5 mg/kg) for 12 SW; Group VIII: AD disease control + baicalein (10 mg/kg) for 12 SW; Group IX: AD disease control + rivastigmine (0.3 mg/kg) for 12 SW. Behavioral test, T-maze, and rotarod test were also performed before and after the treatment. At the end of the experimental study, all the rats were sacrificed and their brains were removed and divided into two portions. The first portion was homogenated for estimating the level of acetylcholinesterase (AchE) and acetylcholine (Ach). Another portion was used for histopathological evaluation. RESULTS: The current investigation showed that baicalein significantly reduced the duration of revolving on the rotarod, cage activity, and T-maze activity in a dose-dependent manner compared with the AD control group rats. It also altered the AchE and Ach levels in the brain homogenates. The histopathology study also provides strength to the protective effect of baicalein. CONCLUSION: The current study showed that baicalein significantly (P<0.05) improved the biochemical and histopathological condition of AD in rats.

Total parenteral nutrition caused Wernicke's encephalopathy accompanied by wet beriberi.

PATIENT: Female, 17 FINAL DIAGNOSIS: Wernicke's encephalopathy Symptoms: Blurred vision • dizziness • nystygmus • tachycardia MEDICATION: - Clinical Procedure: - Specialty: Neurology. OBJECTIVE: Mistake in diagnosis. BACKGROUND: Wernicke's encephalopathy (WE) is an acute and life-threatening illness which is not only seen in alcoholics, but also in persons with poor nutrition lacking thiamine (vitamin B1). CASE REPORT: Here, we presented a case of WE in a patient who received parenteral nutrition without complement of thiamine. Besides neuropsychiatric problems, she also manifested prominent cardiovascular abnormalities, which were consistent with wet beriberi. CONCLUSIONS: This case emphasizes the need for thiamine supplementation in prolonged total parenteral nutrition, and also highlights the awareness of WE in persons with parenteral nutrition lacking thiamine. More importantly, we call for attention to wet beriberi in such persons.

The complement and immunoglobulin levels in NMO patients.

Since the discovery of aquaporin-4 (AQP4) antibody a decade ago, neuromyelitis optica (NMO) has been distinguished from multiple sclerosis (MS). MS mainly features T lymphocyte-oriented autoimmune responses while NMO is more precisely influenced by humoral immunity, among which the complement activation has always been reckoned as an important mechanism. The AQP4 antibody, namely NMO-IgG, adds to new evidence of how complement affects the severity of NMO. We compared the levels of complement (C3, C4, CH50) and immunoglobulins (IgG, IgM, IgA) between NMO patients and controls. Groups with AQP4 antibody positive and negative NMO patients were also compared with controls, respectively, aiming to elaborate on the relationship between complement activation and immunoglobulins. We also compared these indexes together with expanded disability status scale (EDSS) between two different groups in NMO patients and endeavored to figure out their correlations with each other. Complement and immunoglobulins were compared between NMO patients in acute phase and non-acute phase of the disease to find out the level fluctuation of CH50 and other indexes during different stages of NMO. We analyzed NMO patients (n = 88) and controls (n = 44) for IgG, IgM, IgA, other indexes like CH50, C3, C4 have also been explored between the two groups. Furthermore, we investigated whether these antibodies could mediate complement-dependent cytotoxicity. Thus, the NMO patients were split into two groups with or without AQP4 antibody to find out the status of NMO-IgG in the development and severity of the disease. EDSS was used as criteria for the evaluating the seriousness of NMO. Comparison between NMO patients in acute stage and non-acute stage of the disease was also made for a better understanding of the disease. Compared with controls, NMO patients had much higher IgG (13.984 ± 5.981 mg/ml, 11.430 ± 3.254 mg/ml, P < 0.01) but lower CH50 (respectively, 43.55 ± 12.172 U/L, 50.66 ± 12.523 U/L, P < 0.01). While IgG increased in Anti-AQP4 antibody-positive NMO patients, CH50 dropped in this group when compared with AQP4-negative patients. When compared with controls, both of the NMO groups had enhanced IgG and decreased CH50 though only AQP4-positive NMO patients showed significance (IgG 15.004 ± 6.613 mg/ml, 11.430 ± 3.254 mg/ml, P < 0.01) (CH50, respectively, 41.12 ± 12.581U/L, 50.66 ± 12.523 U/L, P < 0.01). C4 was also decreased though without evident significance (0.215 ± 0.118 mg/ml, 0.260 ± 0.133 mg/ml, P = 0.069). Those NMO patients in acute phase (with the course of newly attack of less than 1 month) had increased immunoglobulin (IgG 14.991 ± 6.639 mg/ml, 12.460 ± 4.490 mg/ml) but decreased complement (CH50 42.755 ± 12.403 U/L, 44.743 ± 11.890 U/L) than those who passed the acute phase. There was correlation between IgG and CH50 (R = -0.402, P < 0.01) in NMO patients. Relationship was also found between IgG and EDSS (R = 0.609, P < 0.001), CH50 and EDSS (R = -0.333, P < 0.01). These results indicate that NMO patients had enhanced immunoglobulin in acute phase but decreased complement. The complement was correlated with immunoglobulin. Among the two NMO groups, the complement system was only activated in NMO-IgG positive patients, which might indicate a potential different pathogenetic mechanism in NMO-IgG negative patients. Also, patients' disability of the former group was more serious than their counterparts. Those patients in acute phase obviously had increased immunoglobulin but decreased complement. Thus, we have come to the conclusion that in AQP4-positive NMO patients, immunoglobulin activates complement system, which influences the functions of NMO patients.

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis.

BACKGROUND: Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. METHODS: Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting. RESULTS: The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group. CONCLUSION: Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.

Splenectomy protects experimental rats from cerebral damage after stroke due to anti-inflammatory effects.

BACKGROUND: A recent study demonstrated that the inflammatory response accompanying necrotic brain injury played an important role in stroke. Thus, inhibition of this response may help to stop the expansion of infarcts. It has been also shown that the spleen, a major peripheral immune organ, plays a role in stroke-induced immune responses. This study aimed to establish rat models of middle cerebral artery occlusion (MCAO) and to investigate the effect of splenectomy and possible mechanisms in that rat models. METHODS: Infarct size in a stroke model was measured with the Nissl body staining method, numbers of inflammatory cells in ischemic regions were detected by immunofluorescence staining, and inflammatory factors were assayed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR) in brain homogenates and sera. The significance of differences was determined by one-way analysis of variance (ANOVA) followed by the least significant difference post hoc test. RESULTS: Infarct size in the brain of rats that underwent splenectomies 2 weeks before permanent MCAO ((34.93 ± 3.23)%) was over 50% smaller than that of rats subjected to the stroke surgery alone ((74.33 ± 2.36)%, P < 0.001; (77.30 ± 2.62)%, P < 0.001). Lower numbers of T cells, neutrophils, and macrophages in brain tissue and lower levels of pro-inflammatory cytokines, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, were observed in rats that underwent splenectomies, compared with the two other groups, but splenectomized rats showed higher levels of the anti-inflammatory factor IL-10 in the brain. CONCLUSION: The mechanism(s) by which splenectomy protects brain from damage induced by stroke may correlate with the decreased numbers of inflammatory cells and changes in inflammatory cytokines.

Effects of Naoxintong on atherosclerosis and inducible nitric oxide synthase expression in atherosclerotic rabbit.

BACKGROUND: High levels of nitric oxide (NO) produced by inducible NO synthase (iNOS) have been associated with atherosclerosis processes. Naoxintong is a traditional Chinese medicine for treatment of cerebrovascular and cardiovascular disease. The aim of the present study was to detect and quantify changes of iNOS mRNA and NO levels in the vessel wall after the administration of Naoxintong in an atherosclerotic rabbit model. METHODS: Forty New Zealand white rabbits were randomly divided into five groups (n = 8). Rabbits were fed a standard diet (group A), an atherogenic diet consisting of 79% standard feed + 1% cholesterol + 5% lard + 15% egg yolk powder (group B), an atherogenic diet with Naoxintong 0.25 mg×kg(-1)×d(-1) (group C), an atherogenic diet with Naoxintong 0.5 mg×kg(-1)×d(-1) (group D), or atherogenic diet with Naoxintong 1.0 mg×kg(-1)×d(-1) (group E) for 12 weeks. RESULTS: Supplemented administration of Naoxintong led to a down-regulation of cholesterol (CHOL) (P < 0.001) and low-density lipoprotein (LDL) (P < 0.001). The trend became more notable as the dose of Naoxintong increased; group C vs. group B (CHOL, P = 0.568; LDL-cholesterol (LDL-C), P = 0.119), group D vs. group B (CHOL, P = 0.264; LDL-C, P = 0.027), group E vs. group B (CHOL, P = 0.028; LDL-C, P = 0.002). Atherosclerotic lesions in aorta were reduced in Naoxintong groups (groups C, D, E) compared to group B. Group B had higher iNOS mRNA (P = 0.001) and NO level (P < 0.001) than group A. Compared with the atherogenic diet fed-rabbits, Naoxintong supplements decreased the expression of iNOS mRNA (P < 0.001) and the NO level (P < 0.001) in the vessel wall. Groups given a higher Naoxintong dose exhibited greater benefits. iNOS mRNA and NO levels seemed to be reduced in group C, although the difference did not quite reach statistical significance (iNOS mRNA, P = 0.130; NO, P = 0.038). iNOS mRNA and NO levels significantly decreased in group D (iNOS mRNA, P = 0.019; NO, P = 0.018) and group E (iNOS mRNA, P = 0.004; NO, P < 0.001). CONCLUSION: Naoxintong has beneficial effects on atherosclerosis treatment by reducing expression of iNOS mRNA and the NO level in the vessel wall.

Relationship between neuromyelitis optica-IgG status and spinal cord magnetic resonance imaging in patients with neuromyelitis optica.

BACKGROUND: Despite the large scale technical innovations that have been made, a number of patients with neuromyelitis optica (NMO) are lacking NMO-IgG in both serum and cerebrospinal fluid. Longitudinally extensive spinal cord (LESC) lesions and linear lesions are associated with NMO. However, differences of spinal cord magnetic resonance imaging (MRI) features, including LESC lesions and linear lesions, between NMO-IgG positive and negative patients still remain unknown. The aim of the present study was to analyze the relationship between NMO-IgG status and spinal cord MRI features in NMO patients, particularly concerned about LESC lesions and linear lesions. METHODS: Clinical data and spinal cord MRI of 52 NMO patients were retrospectively analyzed. Eight patients were NMO-IgG negative in both serum and cerebrospinal fluid, while 44 were NMO-IgG positive. Quantitative data between the two cohorts were compared by the Student's t test or Mann-Whitney U test, the chi-square test or Fisher's exact test was used to evaluate qualitative data. RESULTS: NMO-IgG negative patients had a higher sex ratio (male/female) (P = 0.014). On axial MRI, lesions in the NMO-IgG negative group were mostly located in the peripheral cord (50%), and central lesions (55%) were more common in the NMO-IgG positive group (P = 0.051). LESC lesions were common in both cohorts. None of linear lesions was found in NMO-IgG negative patients, while the NMO-IgG positive cohort had significantly more linear lesions (48%) (P = 0.016). CONCLUSIONS: Patients with NMO-IgG negativity may have different spinal cord lesion features compared to NMO-IgG positive patients. Diagnosis of NMO cannot be excluded even when NMO-IgG negativity and non-specific spinal lesions occur.

[An evaluation of clinical characteristics and prognosis of brain-stem infarction in diabetics].

OBJECTIVE: To analyze the relationship between diabetics and the onset, clinical outcomes and prognosis of brainstem infarction, and to evaluate the impact of diabetes on brainstem infarction. METHOD: Compare 172 cases of acute brainstem infarction in patients with or without diabetes. Analyze the associated risk factors of patients with brain-stem infarction in diabetics by multi-variate logistic regression analysis. Compare the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin scale (mRS) Score, pathogenetic condition and the outcome of the two groups in different times. RESULTS: The systolic blood pressure (SBP), TG, LDL-C, apolipoprotein B (Apo B), glutamyl transpeptidase (γ-GT), fibrinogen (Fb), fasting blood glucose (FPG) and glycosylated hemoglobin(HbA1c)in diabetic group were higher than those in non-diabetic group, which was statistically significant (P < 0.05). From multi-variate logistic regression analysis, γ-GT, Apo B and FPG were the risk predictors of diabetes with brainstem infarction(OR = 1.017, 4.667 and 3.173, respectively), while HDL-C was protective (OR = 0.288). HbA1c was a risk predictor of severity for acute brainstem infarction (OR = 1.299), while Apo A was beneficial (OR = 0.212). Compared with brain-stem infarction in non-diabetic group, NIHSS score and intensive care therapy of diabetic groups on the admission had no statistically significance, while the NIHSS score on discharge and the outcome at 6 months' of follow-up were statistically significant. CONCLUSIONS: Diabetes is closely associated with brainstem infarction. Brainstem infarction with diabetes cause more rapid progression, poorer prognosis, higher rates of mortality as well as disability and higher recurrence rate of cerebral infarction.

[Bone marrow stromal cells transfected with ciliary neurotrophic factor gene ameliorates the symptoms and inflammation in C57BL/6 mice with experimental allergic encephalomyelitis].

OBJECTIVE: To investigate the anti-inflammatory effect of bone marrow stromal cells (MSCs) transfected with recombinant adenovirus-mediated ciliary neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic encephalomyelitis (EAE). METHODS: An adenovirus vector containing CNTF gene Ad-CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After examination of CNTF expression, the transfected cells were transplanted in C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha), inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the peripheral blood of the mice were detected, and the number of MSC-CNTF cells in the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha and IFN-gamma expressions in the lesions were also observed after the cell transplantation. RESULTS: CNTF gene transfection resulted in significantly increased CNTF expression in the MSCs. The mice receiving MSC-CNTF transplantation exhibited significantly improved symptoms with shortened disease course and lessened disease severity. The cell transplantation also resulted in significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell infiltrations and lowered TNF-alpha expression in the lesions, while the levels of IFN-gamma underwent no significant changes. CONCLUSION: Transplantation of CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha expression in the lesion of EAE, therefore providing better effect than MSCs in relieving the symptoms of EAE in mice.

Adenoviral delivery of soluble VEGF receptor 1 (sFlt-1) inhibits experimental autoimmune encephalomyelitis in dark Agouti (DA) rats.

Previous studies have shown that vascular endothelial growth factor (VEGF) expression is up-regulated in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), a model for MS, and may exacerbate the disease. However, it remains unknown whether anti-VEGF modalities could serve as a potential treatment for such central nervous system (CNS) autoimmune diseases. We constructed a recombinant adenoviral vector carrying FLAG-tagged sFlt-1(1-3) (the first three extracellular domains of Flt-1, the hVEGF receptor-1). Intramuscular transfection of the recombinant adenoviral vector suppressed VEGF-induced inflammatory cell infiltration in matrigel plugs. When given intracerebrally to EAE rats, recombinant sFlt-1(1-3) adenoviral vector significantly reduced disease severity compared to untreated rats. sFlt-1(1-3) gene transfer blocked VEGF and greatly reduced the number of cells that express VEGF and ED1-positive cells in CNS in EAE rats. This study demonstrates that sFlt-1(1-3) gene transfer into the brain ameliorates the severity of EAE by inhibiting monocyte recruitment in the CNS of dark Agouti rats.