Gastrodin Inhibits Expression of Inducible NO Synthase, Cyclooxygenase-2 and Proinflammatory Cytokines in Cultured LPS-Stimulated Microglia via MAPK Pathways

Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS).BV-2 cells were pretreated with gastrodin (30, 40, and 60 µM) for 1 h and then stimulated with LPS (1 µg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-κB (NF-κB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β and NF-κB. LPS (1 µg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α) (and hence the activation of NF-κB) and of CREB, respectively.This study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases

Selective mGluR1 Antagonist EMQMCM Inhibits the Kainate-Induced Excitotoxicity in Primary Neuronal Cultures and in the Rat Hippocampus

Abundant evidence suggests that indirect inhibitory modulation of glutamatergic transmission, via metabotropic glutamatergic receptors (mGluR), may induce neuroprotection. The present study was designed to determine whether the selective antagonist of mGluR1 (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), showed neuroprotection against the kainate (KA)-induced excitotoxicity in vitro and in vivo. In in vitro studies on mouse primary cortical and hippocampal neuronal cultures, incubation with KA (150 μM) induced strong degeneration [measured as lactate dehydrogenase (LDH) efflux] and apoptosis (measured as caspase-3 activity). EMQMCM (0.1–100 μM) added 30 min to 6 h after KA, significantly attenuated the KA-induced LDH release and prevented the increase in caspase-3 activity in the cultures. Those effects were dose- and time-dependent. In in vivo studies KA (2.5 nmol/1 μl) was unilaterally injected into the rat dorsal CA1 hippocampal region. Degeneration was calculated by counting surviving neurons in the CA pyramidal layer using stereological methods. It was found that EMQMCM (5–10 nmol/1 μl) injected into the dorsal hippocampus 30 min, 1 h, or 3 h (the higher dose only) after KA significantly prevented the KA-induced neuronal degeneration. In vivo microdialysis studies in rat hippocampus showed that EMQMCM (100 μM) significantly increased γ-aminobutyric acid (GABA) and decreased glutamate release. When perfused simultaneously with KA, EMQMCM substantially increased GABA release and prevented the KA-induced glutamate release. The obtained results indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against excitotoxicity after delayed treatment (30 min to 6 h). The role of enhanced GABAergic transmission in the neuroprotection is postulated

Valid and reliable instruments for arm-hand assessment at ICF activity level in persons with hemiplegia: a systematic review

Contains fulltext : 110141.pdf (publisher's version ) (Open Access)BACKGROUND: Loss of arm-hand performance due to a hemiparesis as a result of stroke or cerebral palsy (CP), leads to large problems in daily life of these patients. Assessment of arm-hand performance is important in both clinical practice and research. To gain more insight in e.g. effectiveness of common therapies for different patient populations with similar clinical characteristics, consensus regarding the choice and use of outcome measures is paramount. To guide this choice, an overview of available instruments is necessary. The aim of this systematic review is to identify, evaluate and categorize instruments, reported to be valid and reliable, assessing arm-hand performance at the ICF activity level in patients with stroke or cerebral palsy. METHODS: A systematic literature search was performed to identify articles containing instruments assessing arm-hand skilled performance in patients with stroke or cerebral palsy. Instruments were identified and divided into the categories capacity, perceived performance and actual performance. A second search was performed to obtain information on their content and psychometrics. RESULTS: Regarding capacity, perceived performance and actual performance, 18, 9 and 3 instruments were included respectively. Only 3 of all included instruments were used and tested in both patient populations. The content of the instruments differed widely regarding the ICF levels measured, assessment of the amount of use versus the quality of use, the inclusion of unimanual and/or bimanual tasks and the inclusion of basic and/or extended tasks. CONCLUSIONS: Although many instruments assess capacity and perceived performance, a dearth exists of instruments assessing actual performance. In addition, instruments appropriate for more than one patient population are sparse. For actual performance, new instruments have to be developed, with specific focus on the usability in different patient populations and the assessment of quality of use as well as amount of use. Also, consensus about the choice and use of instruments within and across populations is needed

Robot-assisted task-oriented upper extremity skill training in cervical spinal cord injury: a feasibility study

Study design:Prospective multiple case study.Objectives:To test (1) the feasibility of haptic robot technology (Haptic Master (HM)) use to improve arm-hand function (AHF) and arm-hand skill performance (AHSP) in persons with a cervical spinal cord injury (C-SCI), (2) inventory participants' motivation and expectation to work with the robot technology used and (3) to descriptively report the results in individual cases.Setting:Rehabilitation Centre.Methods:Five C-SCI patients were trained for 6 weeks, 3 days per week, 60 min per day. Therapists filled out the Usefulness, Satisfaction and Ease-of-use questionnaire (USE). The Intrinsic Motivational Inventory (IMI) and credibility and expectancy questionnaire (CEQ) were filled out by participants. Performance at activity level was gauged using the Van Lieshout test for AHF in Tetraplegia and the Spinal Cord Independence Measure. Function level was gauged using muscle strength testing and the International Classification for Surgery of the Hand in Tetraplegia.Results:As to the feasibility of the application of haptic robot technology, the mean USE score was 65%. Mean IMI and CEQ results were 67% and 60%, respectively. Participants were motivated to train with the HM. All participants rated credibility higher than expectations regarding the improvement. In the current patients, little progress was demonstrated at the International Classification of Functioning, Disability and Health function and the activity level.Conclusion:It is feasible to train C-SCI persons with the HM. Therapists report that working with the HM is easy to learn and easy to perform. Usability of the HM may be improved. Further research is needed to assess in which group of C-SCI and at which stage of rehabilitation HM training may be most beneficial.Spinal Cord advance online publication, 3 February 2015; doi:10.1038/sc.2014.250

Evaluation of a task-oriented client-centered upper extremity skilled performance training module in persons with tetraplegia

Study design: Clinical intervention study. Objective: Arm hand skilled performance (AHSP) has a major role in the rehabilitation of persons with cervical spinal cord injury (C-SCI). A task-oriented client-centered upper extremity skilled performance-training (ToCUEST) module was developed. The present study aims to evaluate effects of ToCUEST on specific and general AHSP in C-SCI, during and after rehabilitation. Setting: Adelante Rehabilitation Centre (The Netherlands). Methods: C-SCI persons, either during or after rehabilitation, completed the ToCUEST training; a control group of patients during rehabilitation received standard rehabilitation. The training module was focused on patient's individual needs, combining principles of motor learning and training physiology. Three self-selected goals were trained 3 days per week, in three sessions of 30 min per day for 8 weeks. Measures were taken at 3 months after the start of the active rehabilitation (T0), before training (T1), after training (T2), at follow-up (3 months post-training; T3) and at discharge. Results: For both ToCUEST groups during (n = 11) and after (n = 12) rehabilitation, an improvement (

Reference values for the transformed Van Lieshout hand function test for tetraplegia.

Item does not contain fulltextSTUDY DESIGN: Longitudinal cohort study. OBJECTIVES: Previously, the Van Lieshout hand function test for tetraplegia (short form)(VLT-SF) has been transformed into an interval scale (r_VLT-SF) using the Rasch analysis, thereby fulfilling the requirements of an objective measurement. The present study aims (1) to transform r_VLT-SFlogit scores (r_VLT-SFlogit) into 0-100 scores (r_VLT-SF100) in order to facilitate communication amongst its users and (2) to describe r_VLT-SF100 reference values in order to refine the prediction of upper extremity skilled performance in persons with tetraplegia. SETTING: Eight Dutch rehabilitation centres. METHODS: The VLT-SF data of tetraplegic patients from eight Dutch rehabilitation centres, gathered at the start of the active rehabilitation (t1), 3 months after t1 (t2) and at the time of discharge (t3), have been used. The r_VLT-SF100 total score for t1 and t3 were computed, anchored on the data for t2. Reference values (medians and interquartiles) for different subgroups were calculated at different moments during the rehabilitation. RESULTS: Data at t1 (n=64), t2 (n=73) and t3 (n=69) were used. The r_VLT-SFlogit scores (-4.78-6.32) were transformed into r_VLT-SF100 (0-100) at t2. Reference values were established for persons with motor complete or incomplete lesions with either a high (C1-C6) or a low (C7-T1) lesion level at t1, t2 and t3. Significant differences (P<0.025) in r_VLT-SF100 were found for most subgroups and different time intervals. CONCLUSIONS: The r_VLT-SFlogit scores were converted into r_VLT-SF100 scores, and reference values of the r_VLT-SF100 have been established for different subgroups of tetraplegic patients at different stages during rehabilitation. The r_VLT-SF100 has been proven to be able to detect improvement over time.1 oktober 201

Improvement of the Van Lieshout hand function test for tetraplegia using a Rasch analysis.

Item does not contain fulltextSTUDY DESIGN: Cross-sectional study. OBJECTIVE: The Van Lieshout hand function test for tetraplegia (VLT) measures the quality of arm-hand functioning in persons with tetraplegia. It is valid, reliable and responsive. However, it does not satisfy all the criteria for interval level measurement. The present study aims to apply the Rasch model to the VLT short form (VLT-SF) to upgrade its scale type towards interval level, and to verify if the requirements of an objective measure are satisfied in the revised version. SETTING: Eight Dutch Rehabilitation centres. METHODS: The VLT-SF data of 73 tetraplegic patients were Rasch-analysed (RUMM2030 software, RUMM Laboratory Pty Ltd, Perth, Australia) to verify the order of response categories, unidimensionality and reliability of the VLT-SF, and to assess its applicability regardless of (motor) lesion completeness. RESULTS: Seven of the ten VLT-SF items showed disordered response categories. The six original response categories were therefore recoded into three or four categories. After recoding, all items satisfied the model requirement of unidimensionality. The items were relatively well-targeted on the subjects' arm-hand skilled performance measures, leading to a good person separation index (R=0.91). The difficulty hierarchy of the VLT-SF items was invariant across patient subgroups of (motor) lesion completeness. CONCLUSIONS: Provided that response categories are recoded, VLT-SF Rasch analysis showed that the requirements of an objective measure were satisfied. This allows to compare the measurements of different patients quantitatively, and to follow their results over time.1 oktober 201

ToCUEST: a task-oriented client-centered training module to improve upper extremity skilled performance in cervical spinal cord-injured persons

Objectives: Given (a) the importance of upper extremity skill performance in persons with cervical spinal cord injury (C-SCI), (b) the limited number of studies on arm hand functioning in C-SCI and (c) the discrepancy between the importance of client centeredness and the lack of a theoretical framework and practical guidelines on how to apply client centeredness into practice, the aim of the present study is to (1) develop a training concept in which rehabilitation of the upper extremity focuses on patient's needs and wishes and (2) to put this concept into practice for tetraplegic persons. Methods: The training concept contains two main components. The client-centered component includes both extracting individual goals and defining and objectifying these goals. The task-oriented component incorporates a task analysis and the composition of an individual training program. Results: A task-oriented client-centered training aimed at improving upper extremity skilled performance in tetraplegic persons is described step by step. The Canadian Occupational Performance Measure is used to identify patient's specific needs. The Goal Attainment Scale is applied to define and objectify individual goals. A task analysis is essential to map limiting and facilitating factors of the person, the task and the environment and to identify which aspects should be trained. An individual task-oriented training program is composed, based on principles of motor learning and training physiology and the use of assistive devices. Each step is explained and illustrated using a case example. Spinal Cord (2011) 49, 1042-1048; doi:10.1038/sc.2011.52; published online 31 May 201

Motor training programs of arm and hand in patients with MS according to different levels of the ICF: a systematic review

<p>Abstract</p> <p>Background</p> <p>The upper extremity plays an important role in daily functioning of patients with Multiple Sclerosis (MS) and strongly influences their quality of life. However, an explicit overview of arm-hand training programs is lacking. The present review aims to investigate the training components and the outcome of motor training programs for arm and hand in MS.</p> <p>Methods</p> <p>A computerized systematic literature search in 5 databases (PubMed, CINAHL, EMBASE, PEDro and Cochrane) was performed using the following Mesh terms: Multiple Sclerosis, Rehabilitation, Physical Education and Training, Exercise, Patient-Centered Care, Upper Extremity, Activities of Daily Living, Motor Skills, Motor Activity, Intervention Studies and Clinical Trial. The methodological quality of the selected articles was scored with the Van Tulder Checklist. A descriptive analyses was performed using the PICO principle, including scoring of training components with the calculation of Hedges’g effect sizes.</p> <p>Results</p> <p>Eleven studies were eligible (mean Van Tulder-score = 10.82(SD2.96)). Most studies reported a specific improvement in arm hand performance at the ICF level that was trained at. The mean number of training components was 5.5(SD2.8) and a significant correlation (r = 0.67; p < 0.05) between the number of training components and effect sizes was found. The components ‘client-centered’ and ‘functional movement’ were most frequently used, whereas ‘distribution based practice’, ‘feedback’ and ‘random practice’ were never used. The component ‘exercise progression’ was only used in studies with single ICF body function training, with the exception of 1 study with activity level training. Studies including the component ‘client-centred’ demonstrated moderate to high effect sizes.</p> <p>Conclusion</p> <p>Motor training programs (both at the ICF body function and activity level) have shown to improve arm and hand performance in MS in which the value of the training specificity was emphasized. To optimize upper extremity training in MS the component ‘client-centred’ and ‘exercise progression’ may be important. Furthermore, given the importance attributed to the components ‘distribution based practice’, ‘feedback’ and ‘random practice’ in previous research in stroke patients, the use of these components in arm hand training should be explored in future research.</p