The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model.

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD). Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining. Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms. Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Anti-neuron antibody syndrome: clinical features, cytokines/chemokines and predictors.

BACKGROUND: Neuroimmunology is a rapidly expanding field, and there have been recent discoveries of new antibodies and neurological syndromes. Most of the current clinical studies have focused on disorders involving one specific antibody. We have summarized a class of antibodies that target common neuronal epitopes, and we have proposed the term "anti-neuron antibody syndrome" (ANAS). In this study, we aimed to clarify the clinical range and analyse the clinical features, cytokines/chemokines and predictors in ANAS. METHODS: This was a retrospective cohort study investigating patients with neurological manifestations that were positive for anti-neuron antibodies. RESULTS: A total of 110 patients were identified, of which 43 patients were classified as having autoimmune encephalitis (AE) and the other 67 were classified as having paraneoplastic neurological syndrome (PNS). With regards to anti-neuron antibodies, 42 patients tested positive for anti-N-methyl-D-aspartate receptor (NMDAR) antibody, 19 for anti-Hu, 14 for anti-Yo and 12 for anti-PNMA2 (Ma2). There were significant differences between the ANAS and control groups in serum B cell-activating factor (BAFF) levels and in cerebrospinal fluid (CSF) C-X-C motif chemokine10 (CXCL10), CXCL13, interleukin10 (IL10), BAFF and transforming growth factor ß1 (TGFß1) levels. Predictors of poor outcomes included having tumours (P = 0.0193) and having a chronic onset (P = 0.0306), and predictors of relapses included having lower levels of CSF BAFF (P = 0.0491) and having a larger ratio of serum TGFß1/serum CXCL13 (P = 0.0182). CONCLUSIONS: Most patients with ANAS had a relatively good prognosis. Having tumours and a chronic onset were both associated with poor outcomes. CSF BAFF and the ratio of serum TGFß1/serum CXCL13 were associated with relapses.

Jie-Yu-He-Huan Capsule Ameliorates Anxiety-Like Behaviours in Rats Exposed to Chronic Restraint Stress via the cAMP/PKA/CREB/BDNF Signalling Pathway.

Chronic stress is a critical factor in the aetiology of anxiety disorders; however, in the clinic, enduring and preventive measures are not available, and therapeutic drugs are associated with inevitable side effects. Our study established an anxiety rat model using chronic restraint stress (CRS) and assessed these animals using the open-field test, elevated plus-maze test, and light-dark box test. Jie-Yu-He-Huan capsule (JYHH), a Chinese medicine formula, was used as a preventative drug. The HPA axis-mediated release of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone from the hypothalamus was tested. In the hippocampus and prefrontal cortex, concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid, as well as monoamine oxidase A, glucocorticoid receptor, and 5-HT1A receptor expression levels, were measured. Furthermore, we examined protein and mRNA expression of cAMP-PKA-CREB-BDNF pathway components. The results showed that JYHH had a significant preventative effect on the anxiety-like behaviour induced by CRS and prevented abnormal changes in the HPA axis and 5-HT system. Furthermore, CRS inhibited the cAMP-PKA-CREB-BDNF pathway, which returned to normal levels following JYHH treatment. This might be the underlying molecular mechanism of the antianxiety effect of JYHH, which could provide a new clinical target for preventative anxiolytic drugs for chronic stress.

Establishment and identification of a novel HTRA1 mutation mice model.

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathyis a rare form of inherited cerebral small vessel disease associated with mutations in the high-temperature requirement serine peptidase A1 gene. As of now, only about 50 cases have been reported. In 2012, our group reported a family with a novel mutant of the high-temperature requirement serine peptidase A1 gene in China for the first time. To further explore the molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a recombination mouse model expressed human high-temperature requirement serine peptidase A1 gene mutant identified by our group was generated using the Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 system and termed the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model. Results show that Mut-high-temperature requirement serine peptidase A1 geneL364P mice present similar pathological characteristics to patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting that the Mut-high-temperature requirement serine peptidase A1 geneL364P mouse model was generated successfully. Moreover, apoptosis was induced in mouse brain vascular smooth muscle cells derived from Mut-high-temperature requirement serine peptidase A1 geneL364P mice. In summary, the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy mouse model described in this study will be beneficial to demonstrate the pathological mechanism of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy and provide new therapeutic targets for clinical treatment.

Effect of Surgical Adhesive on the Uterus of Rabbits Following Occlusion.

Purpose/Aim of the Study: The present study investigated the effect of surgical adhesives on the uterus of rabbits and the histomorphology alterations following occlusion, to improve the clinical treatment of abnormal fallopian tube with surgical adhesives for in vitro fertilization and embryo transfer (IVF-ET). Materials and Methods: The experimental rabbits received laparotomy and occlusion of the uterus by surgical adhesive adjacent to the two fallopian tubes, while the control rabbits only received laparotomy. The body weight, hysterosalpingography, and histomorphology were measured to evaluate the uterine occlusion at 1 and 6 months after surgery. Results: There was no significant difference in the mortality rate or body weight between the experimental and control groups. In the experimental group, 38 uterine cavities were identified in 19 rabbits, of which 97.37% were occluded, with expanded uterine cavity and tissue oppression at 1 month after surgery. In total, 33 uterine cavities out of the 36 in the control group were occluded, with proliferation of new stratified epithelial cells observed at 6 months after surgery. In the control group, 20 uterine cavities of 10 rabbits were observed to be absent of occlusion at 1 month after surgery, while 18 uterine cavities in the remaining 9 rabbits were also absent of occlusion at 6 months after the surgery. Conclusion: Surgical adhesives are effective in occluding the uterus of rabbits without adverse effects, supporting their potential clinical use to treat the occlusion in abnormal fallopian tubes prior to IVF-ET.

Corrigendum: Clinical Characteristics and Predictors of Outcome for Onconeural Antibody-Associated Disorders: A Retrospective Analysis.

[This corrects the article DOI: 10.3389/fneur.2017.00584.].

Clinical Characteristics and Predictors of Outcome for Onconeural Antibody-Associated Disorders: A Retrospective Analysis.

Objective: To describe and analyze the clinical characteristics, laboratory data, management, and outcome of patients with onconeural antibody-associated disorders (OAAD) and identify predictors for poor outcome. Methods: This was a retrospective review of all patients with potential OAAD, who were hospitalized in Jinan General Hospital between September 2009 and July 2017. We clarified the diagnosis, collected comprehensive information and categorized patients into three groups: paraneoplastic neurological disorders (PNDs), autoimmune encephalitis (AE), and possible OAAD. Within the three groups, we analyzed a range of clinical and laboratory parameters and used univariate and multivariate regression analysis to identify predictors for poor outcome [modified Rankin Scale (mRS) = 3-6]. Results: From 158 patients, we identified 70 who fulfilled the criteria for OAAD, including 44 men (62.9%) and 26 women (37.1%). There were 38 patients (54.3%) in the PNDs group, 14 patients (20%) in the AE group, and 18 patients (25.7%) in the possible OAAD group. After the last follow-up, 14 (36.8%), 9 (64.2%), and 12 (66.7%) had a good outcome (mRS = 0-2). However, 6 (15.8%), 2 (14.3%), and 3 (16.7%) died, respectively. Univariate analysis showed that duration prior to the hospital (p = 0.0224) and urinary incontinence/retention (p = 0.0043) were associated with poor outcome (mRS = 3-6). After multivariate regression analysis, urinary incontinence/retention (p = 0.0388) and an immunocompromised state (p = 0.0247) remained as significant factors for poor outcome. Conclusion: Urinary incontinence/retention and an immunocompromised state represent significant predictors of a worse prognosis for patients with OAAD. By contrast, the results showed that [corrected] cerebrospinal fluid analysis, serum autoantibodies and tumor markers, [corrected] the function of crucial organs, electrophysiology, and radiological findings were not associated with a poor outcome.

Effect of ulinastatin, a human urinary protease inhibitor, on heatstroke-induced apoptosis and inflammatory responses in rats.

Ulinastatin has been demonstrated to protect against heatstroke by reducing cerebral ischemia and damage in rats. In order to extend these observations, apoptosis and systemic inflammatory responses were assessed in rats treated with ulinastatin prior to the initiation of heatstroke. Following the onset of heatstroke, histological analysis revealed that the hippocampal tissues displayed edema and damage. In addition, upregulation of malondialdehyde, inducible nitric oxide synthase (iNOS) and reactive oxygen species and downregulation of superoxide dismutase were observed compared with the respective levels in the control group. Furthermore, TUNEL staining and western blotting assays indicated that heatstroke induced cell apoptosis by increasing the Bax/Bcl-2 ratio and caspase-3 levels, and upregulating the protein expression levels of nuclear factor-κB, cyclooxygenase-2 and iNOS. However, the injury induced by heatstroke was significantly inhibited by ulinastatin pretreatment at doses of 5,000 and 10,000 IU/kg. Survival analysis of the rats subjected to heatstroke demonstrated that rats treated with ulinastatin at a dose of 10,000 IU/kg lived longer than those that did not receive ulinastatin treatment. These observations indicate that ulinastatin may protect against heatstroke by reducing apoptosis and systemic inflammatory responses.

Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29.

Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus.

JAK2/STAT3 pathway mediating inflammatory responses in heatstroke-induced rats.

Heatstroke not only directly induces cell injury, but also causes large amounts of inflammatory mediators release and cells with extensive biological activities to induce a systemic inflammatory response and immune dysfunction. This study aimed to observe the effects of JAK2 inhibitor AG490 on the brain injury and inflammatory responses of rats with systemic heatstroke. Under the light microscope, the hippocampus tissues of rat with heatstroke were edema and apoptotic rate was increased. Up-regulation of malondialdehyde (MDA), nitric oxide synthase (iNOS), reactive oxygen species (ROS) and down-regulation of superoxide dismutase (SOD) were also found after heatstroke in rats, which compared with that of the control group. Heatstroke induced inflammation factors secretions and up-regulated levels of matrix metallopeptidase 2 and 9 (MMP2 and MMP-9) and systemic inflammatory response molecules including intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-beta 1 (TNF-ß1) and cyclooxygenase-2 (COX-2). However, the JAK2 inhibitor AG490 was significantly attenuated the brain injury and inflammatory responses induced by heatstroke in rats. The survival time of heatstroke rats showed that AG490 notably lived longer than heatstroke rats without AG490 treatment. These findings suggest that AG490 may prevent the occurrence of heatstroke via inhibiting the JAK2/STAT3 pathway and the systemic inflammatory responses.