Field Of Neurological Disorders Research Articles

Age-related change of GLP-1R expression in rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4

The glucagon-like peptide-1 receptor (GLP-1R) has been demonstrated as a potential therapeutic target for some neurological diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke. Besides, its distribution and density in brain regions are closely associated with cognition, motor function, learning and memory. Given the relationship between age and these neurological diseases, we firstly examined the influences of age on GLP-1R expression using [18F]AlF-NOTA-MAL-Cys39-exendin-4 microPET imaging. The image showed that GLP-1R expression in nearly all regions of the brain of aged rats was evidently lower than that of normal rats. Significant differences were found in olfactory, striatum, hypothalamus, substantial nigra, and hippocampus, which have inseparable relations with some mental and neurological diseases such as PD and AD. Data obtained from biodistribution and immunohistochemistry staining also confirmed the image results. Taken together, these results illustrated decreased expression of GLP-1R in the brain of aged rats can be detected by [18F]AlF-NOTA-MAL-Cys39-exendin-4, which implied GLP-1R as a reliable target and GLP-1R PET imaging could be a promising technology in the field of neurological diseases.

On status epilepticus and pins: A systematic content analysis.

Status epilepticus (SE) can be defined as abnormally prolonged, persistent, or recurrent clinical and/or electrographic epileptic activity and, as such, is a challenging medical emergency requiring an aggressive treatment aimed at promptly terminating the seizures. It imposes a relevant clinical burden, both in terms of comorbidity and mortality. In the era of the Web 2.0, most people search the Web to obtain SE-related information. The current investigation aimed at qualitatively characterizing the pins related to SE: Pinterest, "the world's catalog of ideas", is a visual social networking site that enables users to freely upload visual material, to bookmark, and to share it (repin). Using SE as a keyword, 192 pins were extracted and analyzed on the basis of their content. Fifty-five were found to meet the inclusion criteria. Fifty-six point four percent of the pins reported at least one cause of SE, the most quoted of which being remote brain injuries (47.3% of the pins); 54.5% and 45.5% of the included pins reported SE symptoms and diagnosis, respectively; 72.7% and 40.0% of pins focused on SE treatment and on prognosis, respectively; and 50.9%, 30.9%, and 40.0% of the pins were intended for physicians, medical/nursing students, and lay people, respectively. Only 12.7% of pins were patient-centered and devoted to fund-raising and advocacy. In the field of neurological diseases, Pinterest, despite being a "pinstructive" tool, is too much overlooked and underused for advocacy purposes. Healthcare workers and stakeholders should be aware of the opportunities offered by Pinterest and exploit this visual social networking site for raising awareness of the life-threatening condition of SE, promoting fund-raising campaigns.

Shape-Memory Terpolymer Rods with 17-β-estradiol for the Treatment of Neurodegenerative Diseases: an In Vitro and In Vivo Study.

PurposeEstradiol (E2)-loaded poly(L-lactide-co-glycolide-trimethylenecarbonate) (P(L-LA:GA:TMC)) rods with shape-memory were developed for the treatment of neurodegenerative diseases. Usefulness of the extrusion method in the obtaining process was also considered. The influence of structural and surface properties during hydrolytic degradation was developed. The possible therapeutic aspect of rods with E2 was determined.MethodsThe extruded rods were incubated in a PBS solution (pH 7.4, 37°C, 240 rpm). The amount of released E2 in vitro conditions was estimated by UV-VIS method. The following methods in the degradation of rods were applied: NMR, DSC, FTIR, GPC, SEM, and optical microscopy. Changes in water uptake and weight loss were also determined. In vivo study was performed on rats. Measurements of E2 level were performed before and after ovariectomy of rats using ELISA method. A sample of tissue adjacent to the site of the rod implantation was analysed under an optical microscope.ResultsA stable and steady degradation process ensured zero-order release of E2. The in vivo study indicated a significant increase in the E2 level in serum after ovariectomy. Moreover, structural and surface features indicated that the extrusion method was appropriate for obtaining E2-loaded rods.ConclusionsShape-memory P(L-LA:GA:TMC) rods with E2 are an adequate proposal for further research in the field of neurological disorders.

Inter-Rater Agreement in the Clinical Diagnosis of Cognitive Status: Data from the Neurological Disorders in Central Spain 2 Pilot Study

Background: To assess the diagnostic agreement of cognitive status (dementia, mild cognitive impairment (MCI), normal cognition) among neurologists in the field of neurological disorders in Central Spain 2 study. Methods: Full medical histories of 30 individuals were provided to 27 neurologists: 9 seniors, 10 juniors and 8 residents. For each case, we were asked to assign a diagnosis of dementia, MCI or normal cognition using the National Institute on Aging-Alzheimer's Association workgroup (NIA-AA) core clinical criteria for all-cause dementia, Winblad et al. criteria for MCI, and analyze intensity and etiology if dementia was diagnosed. Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics. Results: Overall inter-rater agreement on cognitive status was κ = 0.76 (95% CI 0.65-0.86), being slightly higher among junior neurologists (κ = 0.85, 95% CI 0.73-0.95) than among seniors (κ = 0.71, 95% CI 0.59-0.83) and residents (κ = 0.69, 95% CI 0.54-0.81) but without statistical significance among groups. Dementia severity showed an overall κ of 0.34, 0.44 and 0.64 for mild, moderate and severe dementia respectively. Conclusions: Substantial agreement was demonstrated for the diagnosis of cognitive status (dementia, MCI and normal cognition) among neurologists of different levels of experience in a population-based epidemiological study using NIA-AA and Winblad et al. criteria. The agreement rate was lower in the diagnosis of dementia severity.

Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications.

Many central nervous system (CNS) diseases including stroke, spinal cord injury (SCI), and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

Stem-cell therapy for neurologic diseases

AbstractWith the advent of research on stem cell therapy for various diseases, an important need was felt in the field of neurological diseases. While congenital lesion may not be amenable to stem cell therapy completely, there is a scope of partial improvement in the lesions and halt in further progression. Neuro degenerative lesions like Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis have shown improvement with stem cell therapy. This article reviews the available literature and summarizes the current evidence in the various neurologic diseases amenable to stem cell therapy, the plausible mechanism of action, ethical concerns with insights into the future of stem cell therapy.

Multiple facets of poly(ADP-ribose) polymerase-1 in neurological diseases.

Multiple facets of poly(ADP-ribose) polymerase-1 in neurological diseases.

Intracellular Expression of Neurotrophic Factors in Mononuclear Cells of Cord Blood and G-CSF-Mobilized Peripheral Blood As a Potential Source for Cellular Therapy

Purpose: To investigate a possible therapeutic mechanism for cell therapy in the field of neurological disorders using mobilized peripheral blood mononuclear cells (mPBMCs), we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and mPBMCs from children with cerebral palsy (CP) to those from healthy adult donors and to cord blood (CB) donated from healthy newborns.Methods: We evaluated the intracellular expression of neurotrophic factors and inflammatory cytokines in PBMCs and mPBMCs from 14 CP children and 14 healthy adult volunteer donors as well as CB mononuclear cells (CB-MNCs) donated from healthy newborns. For mPBMC, granulocyte colony stimulating factor (G-CSF, 10μg/kg/day) was administered subcutaneously for five consecutive days, and apheresis was performed on the fifth day to collect mPBMC via a central venous catheter. Both PBMC collected prior to G-CSF administration and apheresed mPBMC were cryopreserved. We performed flow cytometric analysis with intracellular staining for various cytokines after thawing PBMCs and mPBMCs as well as CBs.Results: No significant differences in expression of neurotrophic factors were found between PBMC and mPBMC. However, in cells from CP children, the expression of IL-6 was significantly increased in mPBMC as compared to PBMC, and IL-3 was significantly decreased in mPBMC as compared to PBMC. In healthy adults, the expression of both IL-1β and IL-6 were significantly increased in mPBMC as compared to PBMC. The expression of BDNF in mPBMC from CP children was significantly higher than in CB or mPBMC from healthy adults. The expression of G-CSF in mPBMC from CP children was comparable to that in CB but significantly higher than in mPBMC from healthy adults. Lower expression of IL-1β, IL-3, and IL-6 and higher expression of IL-8 and IL-9 was observed from CB and mPBMCs from CP children rather than in healthy adults. Lower expression of IL-1β, and higher expression of IL-8 was observed from mPBMCs from CP children rather than in healthy adults.Conclusion: The altered expression of neurotrophic factors and anti-inflammatory cytokines in mPBMC in CP children and CB from healthy children could provide a new potential source for cellular therapy for individuals with neurologic diseases. DisclosuresLee:Korea Healthcare Technology R&D Project (A101712), Ministry for Health & Welfare, Republic of Korea: Research Funding.

The small heat shock protein HspB8: role in nervous system physiology and pathology.

The accumulation and aggregation of misfolded proteins can be highly cytotoxic and may underlie several human degenerative diseases characterized by neuronal inclusions such as Alzheimer's, Parkinson's, prion-like and polyglutamine repeat diseases. In this context small heat shock proteins, molecular chaperones known to be induced by cell stress, play a fundamental role by facilitating folding of nascent polypeptides, preventing aggregation of misfolded proteins and enhancing their degradation. A recently identified member of the small heat shock protein family, HspB8, is of particular interest in the field of neurological diseases since mutations in its sequence correlate with development of distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. HspB8 expression has been detected in neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington disease and spinocerebellar ataxia type 3. In the latter, HspB8 appears to be involved in protecting the cell from accumulation of insoluble aggregates either by preventing aggregation or by promoting degradation of improperly folded proteins. These data propose that HspB8 may be a major player in the neuroprotective response and a promising target for the development of therapeutic strategies.

In vitro neurogenesis: development and functional implications of iPSC technology.

Neurogenesis is the developmental process regulating cell proliferation of neural stem cells, determining their differentiation into glial and neuronal cells, and orchestrating their organization into finely regulated functional networks. Can this complex process be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology? Can neurodevelopmental and neurodegenerative diseases be modeled using iPSCs? What is the potential of iPSC technology in neurobiology? What are the recent advances in the field of neurological diseases? Since the applications of iPSCs in neurobiology are based on the capacity to regulate in vitro differentiation of human iPSCs into different neuronal subtypes and glial cells, and the possibility of obtaining iPSC-derived neurons and glial cells is based on and hindered by our poor understanding of human embryonic development, we reviewed current knowledge on in vitro neural differentiation from a developmental and cellular biology perspective. We highlight the importance to further advance our understanding on the mechanisms controlling in vivo neurogenesis in order to efficiently guide neurogenesis in vitro for cell modeling and therapeutical applications of iPSCs technology.

Infodemiology and Infoveillance of Multiple Sclerosis in Italy

Multiple Sclerosis (MS) is a chronic debilitating disease of probable autoimmune inflammatory nature, whose aetiology is not fully understood, despite the many efforts and investigations. In this manuscript, we review the concept of “Multiple Sclerosis 2.0”, that is to say the Internet usage by MS patients, for seeking health and disease-related material for self-care and self-management purposes, and we introduce a Google Trends-based approach for monitoring MS-related Google queries and searches, called MS infodemiology and infoveillance. Google Trends has already proven to be reliable for infectious diseases monitoring, and here we extend its application and potentiality in the field of neurological disorders.

Case management of a person with disorders of language and identification of case managers in rehabilitation

The main neurological and neuropsychological disorders related to vascular attacks or strokes, chronic degenerative diseases such as Parkinson or Althaimer, incidental factors such as cranial cerebral trauma, cognitive decline of elderly, occupy a large part of the clinic of the speech therapist because of aspects of specific competence (communicative, cognitive-linguistic and oral functions). Deficits such as aphasia, dyspraxia, dementia, unravelling and other neuropsychological disorders are conditions that necessarily require a multidisciplinary intervention. Rehabilitation, with whole culture of disability related to it, is configured as the central aspect of doing rehabilitation that is related to the activity of the “person” in its entirety and complexity. The concept of “quality of care” presents the citizen as the center of interest for operators called to carry out an increasingly effective, timely, continuous, secure, appropriate practice( with respect to interpersonal communication centralizing the assisted ). The competence of the speech therapist consists of three components: the knowledge, the skills, the behavior; that “knowing how to act “on the whole that guarantees quality, that allows the identification of the best practice through the use of multidisciplinary and professional operational tools, that amends and aligns the behavior of professionals. The proper assessment with standardized instruments is also important, which bring forth the objectives in the short, medium and long term. In the field of neurological diseases in adults, unfortunately dramatic expectations are reported in the response to early therapy, particularly in our more disadvantaged region, with the phenomena of migration. In an alarming situation, there are, however, important experiences and centers of excellence also qualified by the virtuosity of many professionals who collaborate in quickly operational teams rehabilitation, also with the involvement of users’ associations. Aim of the seminary is to compare the forces still operative in the field spatial with other operations experienced in other regions, for the sharing of an uniform model of the “management of the elderly patient in our region” and consequent testing of validity. All repecting the Guidelines and recommendations resulting from the study of the scientific evidence that in the last two years involved authoritative representatives of the profession, scientific societies and organizations representing national.

Intercompany meeting of the health professions

The rehabilitation, within the whole culture of disability, is configured as the central moment of doing rehabilitation which is related to the activity of the “person” in its entirety and complexity. The concept of “ quality of care” reported the citizen at the center of interest of operators called to play a practice increasingly effective, timely, continuous, secure, appropriate (respecting the centrality of the assisted). The theme of neurological diseases, which affect the adult compromising important functions for the quality of life, is a field of great interest for the speech- therapy clinic, amplified in recent years by epidemiological data and incidence of disease responsible for these deficits. “Aging isn’t in itself a disease”: today the elderly independent people unable to manage themselves play meaningful social rules. In Europe, in all nation as well as in our region, taking in the challenge of the aging well, mean especially invest in preventive health policies. Unfortunately though this seems an established fact, seems that this situation is not addressed in a constructive manner. Estimate that the percentage of population over 65 age of years, will reach 34,4% in 2050. Those over 80 should reach 14.2% compared to 4.3% today. This sort of demographic revolution reinforces the right the right to health enshrined by the Constitution and meanwhile infuses law the duty to sustain it over time. The lengthening of life expectancy should be evaluated with optimist although parallel will increase the absolute number of people with severe limitations. Therefore are indispensable various preventive and curative interventions that society will impose. Seems clear that this situation must be addressed and monitored for resource planning and supply of care services, employees in large part of health systems’ budgets, often intended to contain and rationalize the expenditure. In the field of neurological diseases of the adults, unfortunately are reported dramatic expectations in the answer of taken charge, particularly in our region, the most disadvantaged, where there is the phenomenon of migration. In an alarming situation, there are, however, important experiences and centers of excellence also qualified by the virtuosity of many professionals who collaborate in teams rehabilitation, quickly operational, with involvement also of users’ associations. Agency professional in carrying out the activities of its sole responsibility to be seen in a perspective of collaboration with other professional, in a total commitment to the political, civil, scientific sphere raises uniting the provision of public services and the guarantee systems for users.

Validation du CHIP (questionnaire de coping) dans une population française atteinte de maladies neurologiques

Introduction While conceived in the 1960's by Lazarus, the concept of coping was a long time coming in the field of neurological diseases. So far, no valid instrument has been available in French for assessing the style of coping of patients with neurological diseases. Methods We used Coping with Health Injuries and Problems (CHIP), which was conceived for patients with chronic diseases. We proceeded to a factorial analysis in a population of 307 patients with multiple sclerosis (MS) or Parkinson's disease (PD) in order to identify the factors observed in this population. Results We finally retained a model with six factors, which saturated on 24 items and explained 48% of the total variance. Factors we found included palliative coping and distraction, both known for the original instrument, and four new factors: emotional regulation, seeking of well-being/self-preservation, seeking of information and cognitive avoidance. Discussion Tools for assessing coping in a setting of chronic diseases must be adapted to specific diseases. In this new validation, CHIP appeared to be well adapted to the specific features of neurological disorders. This instrument would be useful for the neurologist to better understand the specific ways by which patients cope with their disease. Such knowledge would certainly have a positive effect on the patient-neurologist relationship. Moreover, a better understanding of patients’ coping strategies in neurological diseases could pave the way for specific preventive interventions focusing on using coping strategies to promote better adaptation.