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1.
Clin Immunol ; 230: 108815, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34339843

RESUMO

Traumatic Brain Injury (TBI) is the most prevalent of all head injuries. Microglia play an essential role in homeostasis and diseases of the central nervous system. We hypothesize that microglia may play a beneficial or detrimental role in TBI depending on their state of activation and duration. In this study, we evaluated whether TBI results in a spatiotemporal change in microglia phenotype and whether it affects sensory-motor or learning and memory functions in male C57BL/6 mice. We used a panel of neurological and behavioral tests and a multi-color flow cytometry-based data analysis followed by unsupervised clustering to evaluate isolated microglia from injured brain tissue. We characterized several microglial phenotypes and their association with cognitive deficits. TBI results in a spatiotemporal increase in activated microglia that correlated negatively with spatial learning and memory at 35 days post-injury. These observations could define therapeutic windows and accelerate translational research to improve patient outcomes.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Disfunção Cognitiva/etiologia , Microglia/fisiologia , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/psicologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Citometria de Fluxo , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Microglia/classificação , Microglia/patologia , Modelos Neurológicos , Modelos Psicológicos , Dinâmica não Linear , Aprendizagem Espacial/fisiologia , Memória Espacial/fisiologia , Análise Espaço-Temporal , Pesquisa Médica Translacional
2.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208666

RESUMO

Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Suscetibilidade a Doenças , Hemorragia/etiologia , Fatores Etários , Animais , Biomarcadores , Biópsia , Lesões Encefálicas Traumáticas/diagnóstico , Modelos Animais de Doenças , Eletroencefalografia , Proteína Glial Fibrilar Ácida/metabolismo , Hemorragia/diagnóstico , Imuno-Histoquímica , Aprendizagem em Labirinto , Neurônios/metabolismo , Ratos
3.
Mult Scler Relat Disord ; 53: 103041, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34051694

RESUMO

OBJECTIVE: To explore prospectively through OCT the rate of retinal layer changes in relapsing-remitting multiple sclerosis patients followed up on fingolimod or interferon, as well as the treatments' differential effects on cognitive tests scores. METHODS: This prospective observational study enrolled 128 stable RRMS patients treated either with fingolimod (n = 71) or interferon (n = 56). Symbol-Digit Modality Test and retinal OCT scans were obtained at baseline and every 6 to 12 months. A subgroup of patients underwent expanded cognitive tests annually (Brief visual-spatial memory-total recall, BVMT-delayed recall, and Montreal Cognitive Assessment). Retinal-OCT scans were also obtained from 22 age- and sex-matched healthy controls. Mixed effects regression was used to study annualized changes in retinal layers and cognitive function, including differences between treatment groups. Correlations between annualized changes in retinal measurements and cognitive scores were also explored. RESULTS: Fingolimod treated patients showed no significant difference in the rate of thinning of all retinal layers when compared to healthy controls and had significantly less GCIPL thinning when compared to interferons. SDMT scores improved similarly among both RRMS treatment groups. However, interferon but not fingolimod treated patients had significant decline in MOCA and total recall scores. We also found correlations between the annualized change in GCIPL thickness and annualized change in MOCA scores, and similar correlations with annualized change in total recall scores. CONCLUSION: Fingolimod has a potential role in reducing retinal neurodegeneration in RRMS. Longitudinal OCT measures appear to be sensitive to changes in cognitive function and may be useful for monitoring neuroprotective therapies.


Assuntos
Cloridrato de Fingolimode , Esclerose Múltipla Recidivante-Remitente , Cognição , Cloridrato de Fingolimode/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Interferons , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Testes Neuropsicológicos
4.
Int Nurs Rev ; 68(1): 1-8, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33891770

RESUMO

The World Health Organization designated last year as the International Year of the Nurse and the Midwife. And as we know worldwide, 2020 became an unforgettable year as nurses and midwives everywhere confronted the COVID-19 pandemic. To be a nurse in 2020 was challenging and heroic, but being a nurse in 2020 in Beirut, Lebanon was so extraordinarily charged with adversity. The country witnessed in a one-year series of tragedies of epic dimensions - laying a heavy toll on front-line nurses. We present our stories as eight Lebanese nurses, giving voice to our incredible experiences and our ongoing resilience in the face of these adversities. We served in the emergency department of a Beirut city hospital after a catastrophic explosion occurred in the capital on the 4th of August 2020. We reported for duty during a disaster of immense magnitude and are now coping with the aftermath of trauma. As nurses, we have faced many traumas in our country that has experienced through war and terrorism for decades. Arising from this disaster and challenges of the pandemic, we give policy recommendations that deserve urgent attention in Lebanon and underscore the need for disaster preparation, funding, education and importantly mental health care for nurses and other health professionals with help and support of the international community.


Assuntos
COVID-19/epidemiologia , Recessão Econômica , Explosões , Papel do Profissional de Enfermagem , Atitude do Pessoal de Saúde , Planejamento em Desastres , Humanos , Líbano/epidemiologia , Incidentes com Feridos em Massa , Pandemias , SARS-CoV-2
5.
J Prof Nurs ; 37(2): 387-390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867095

RESUMO

Measurement is at the core of the research process. At the PhD level, students need to develop an in-depth understanding of measures relevant to their area of work and refine their knowledge of measurement issues. Traditionally, measurement coursework in Nursing focused on the psychometric evaluation of instruments measuring cognition and behavior. However, in the age of Big Data, precision medicine, and translational science, PhD students need to develop knowledge and skills relevant to these fields and to collaborate with experts from the different disciplines. Therefore, Nursing faculty need to recognize the state-of-the-science of nursing research and tend to a variety of measurement issues across a spectrum of operationalized concepts. Herein we present an overview of learning outcomes, instructional content and methods of delivery for a contemporary PhD-level course on measurement for Nursing Science. We also present our experience in the design, implementation, and evaluation of a novel PhD measurement course.


Assuntos
Educação de Pós-Graduação em Enfermagem , Pesquisa em Enfermagem , Humanos , Aprendizagem , Estudantes
6.
J Int Neuropsychol Soc ; : 1-10, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33563350

RESUMO

OBJECTIVE: Multiple sclerosis (MS) is often associated with cognitive deficits. Accurate evaluation of the MS patients' cognitive performance is essential for diagnosis and treatment recommendation. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS), widely used cognitive testing battery, examines processing speed, verbal and visuospatial learning, and memory. Our study aims to examine the psychometric properties of an Arabic version of the BICAMS and to provide normative values in a Lebanese sample. METHOD: The BICAMS, comprised of the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R), and a newly developed verbal learning/memory test, the Verbal Memory Arabic Test (VMAT), were administered on healthy subjects and MS patients. The sample consisted of 180 healthy individuals, of whom 63 were retested after 2-3 weeks. Forty-three MS patients matched with 43 healthy subjects based on age, sex, and years of education were assessed. A sample of 10 MS patients was also examined on two occasions. Test-retest reliability and criterion-related validity were examined, and regression-based norms were derived. RESULTS: The test-retest correlations showed good evidence of reliability with coefficients ranging between 0.64 and 0.73 in the healthy sample, and between 0.43 and 0.92 in the MS sample. The BICAMS was able to discriminate between MS patients and matched healthy participants on the SDMT and BVMT-R. Normative data were comparable to other studies. CONCLUSIONS: This new Arabic version of the BICAMS shows initial good psychometric properties. While good evidence of VMAT's reliability was shown in the healthy participants, less test-retest reliability in this tool was seen in the MS group, and partial criterion-related validity was evident. This renders further examination of the VMAT. We provide regression-based norms for a Lebanese sample and encourage the use of this battery in both research and clinical settings.

7.
J Clin Exp Neuropsychol ; 42(5): 505-515, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32567997

RESUMO

BACKGROUND: Tests of verbal memory (list learning) are particularly useful for clinicians and researchers globally, yet there are no psychometrically robust tests that are built indigenously for Arabic-speaking populations, which comprise more than 370 million. OBJECTIVE: To develop a verbal memory Arabic test using a systematic procedure of item selection and then provide evidence of validity and reliability in an Arabic-speaking sample in Lebanon. METHOD: In study 1, we conducted a word prototypicality study (n = 77), and identified 932 words across 7 semantic categories. Following quantitative analyzes and qualitative judgments by an expert panel, we selected a sufficient number of words and categories, and constructed and piloted the items, instructions, and protocol for the Verbal Memory Arabic Test (VMAT). In study 2, we administered the VMAT on a community sample (n = 199; screened for depression and cognitive impairment) and patients with Multiple Sclerosis (n = 16). RESULTS: Scores decreased with age as expected, they discriminated well between healthy and clinical populations (matched on age, sex, and years of education), and showed acceptable consistency within items and across time. Conclusions: The VMAT is the first Arabic test developed indigenously. It can be used in clinical and research settings with Arabic-speaking populations to assess verbal learning.


Assuntos
Disfunção Cognitiva/diagnóstico , Testes de Memória e Aprendizagem/normas , Psicometria/normas , Aprendizagem Verbal , Adulto , Árabes , Disfunção Cognitiva/etiologia , Depressão/complicações , Feminino , Humanos , Líbano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Projetos Piloto , Psicometria/instrumentação , Psicometria/métodos , Valores de Referência , Reprodutibilidade dos Testes , Aprendizagem Verbal/fisiologia
8.
Biochem Pharmacol ; 178: 114041, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32439335

RESUMO

Prediabetes is a highly prevalent stage of early metabolic dysfunction that poses a high risk for cardiovascular and cognitive impairment without a clear pathological mechanism. Here, we used a non-obese prediabetic rat model previously developed in our laboratory to examine this mechanism. These rats were subjected to a mild metabolic challenge leading to hyperinsulinemia without hyperglycemia or obesity. This was associated with impaired hippocampal-dependent cognitive functions together with an augmented cerebrovascular myogenic tone. Consequently, hippocampal expression of hypoxia-inducible factor-1α increased, together with markers of mitochondrial dysfunction and oxidative stress. In parallel, the phosphorylation of Akt and mTOR increased in the prediabetic rat hippocampus alongside increased expression of p62 and LC3 puncta indicating a possible repression of autophagic flux. Neuroinflammation and neuronal apoptosis were detected in the hippocampal CA1 area as increased CD68 and IBA-1 staining, as well as increased TUNEL staining and caspase-3 activity, respectively. Treatment with metformin or pioglitazone, at a previously determined vasculoprotective non-hypoglycemic dose, reversed the cerebrovascular and hippocampal molecular alterations and ameliorated cognitive function. The present study proposes a mechanistic framework whereby prediabetic cerebrovascular impairment potentially leads to a mild hypoxic state that is exacerbated by the metabolic dysfunction-driven suppression of neuronal autophagy leading to cognitive impairment.


Assuntos
Autofagia/fisiologia , Barreira Hematoencefálica/metabolismo , Transtornos Cerebrovasculares/metabolismo , Disfunção Cognitiva/metabolismo , Hipoglicemiantes/uso terapêutico , Estado Pré-Diabético/metabolismo , Animais , Autofagia/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Transtornos Cerebrovasculares/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Hipoglicemiantes/farmacologia , Masculino , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/metabolismo , Estado Pré-Diabético/tratamento farmacológico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
9.
J Steroid Biochem Mol Biol ; 200: 105628, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32061642

RESUMO

Multiple Sclerosis (MS) is often associated with low serum 25(OH)D levels, as well as cognitive dysfunctions. The relationship between 25(OH)D and the most commonly affected cognitive domain in MS; processing speed, is poorly explored. The purpose of this study is to: (1) assess the effect of serum 25(OH)D change on processing speed in MS, and (2) explore the relationship between serum 25(OH)D and brain volume changes in MS. A retrospective chart review was conducted, data from 299 patients were extracted (baseline), of whom 163 had follow-up measurements (after at least a 9-month interval). The Symbol Digits Modalities Test (SDMT) was used as a measure of processing speed. MRI data was available from 78 individuals at baseline, and 70 at follow-up. SDMT scores and brain volumes (Cerebellum (total, grey, and white), intracranial, Grey Matter (GM), and White Matter (WM)) were compared based on 25(OH)D levels and their changes towards follow-up. Results indicated that patients with deficient 25(OH)D levels had lower SDMT scores when compared to those with sufficient levels, and SDMT scores improved as a function of 25(OH)D. For MRI measures, only patients with sufficient 25(OH)D levels during both assessment periods had significant changes in intracranial and total cerebellum volumes. We conclude that 25(OH)D levels seem to have an effect on processing speed in MS, thus the importance of clinical monitoring and supplementation in this regard is reinforced.


Assuntos
Disfunção Cognitiva/sangue , Esclerose Múltipla/sangue , Vitamina D/sangue , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico por imagem , Testes Neuropsicológicos , Adulto Jovem
10.
Mult Scler J Exp Transl Clin ; 6(1): 2055217319848467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31976081

RESUMO

Background: In the Middle East and North Africa (MENA) region, few studies explored the quality of life of multiple sclerosis patients and the factors affecting it. Objective: The objective of this study was to explore studies on multiple sclerosis quality of life in the MENA area through a comprehensive literature review. To validate the Multiple sclerosis international Quality of Life (MusiQoL) and Modified Fatigue Impact Scale (MFIS) in Arabic, and investigate the impact of sociodemographic and clinical variables of Lebanese multiple sclerosis patients on quality of life. Methods: As part of an ongoing observational prospective research study, data from 663 stable multiple sclerosis patients were analysed. Results: In Lebanese multiple sclerosis patients, the Arabic MusiQoL and MFIS seem to be accurate and valid tools with high reliability coefficients and confirmatory factor analytic indices. Variables such as age and disease type predicted multiple sclerosis quality of life, yet were significantly affected by psychosocial fatigue. The influence of sociodemographic and clinical variables on quality of life dimensions varied. Being a woman with multiple sclerosis, receiving medications and experiencing physical fatigue worsens the psychological wellbeing quality of life dimension. Conclusion: Several sociodemographic and clinical variables predicted the health-related quality of life dimensions of multiple sclerosis patients in MENA. Further in-depth investigation to guide more targeted clinical management is recommended. We encourage using validated multidimensional tools to measure quality of life in MENA such as the Arabic MusiQoL.

11.
Methods Mol Biol ; 2011: 383-392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273711

RESUMO

Traumatic brain injury (TBI) is one of the most frequent causes of brain damage. Cognitive deficits have been reported in the literature after mild-to-severe TBI affecting memory, language, executive functions, attention, and information processing speed. In this chapter, we describe a method to characterize cognitive impairment in rats following TBI of various intensities. The focus will be on spontaneous object recognition and temporal order memory in rats. These tests are performed in a Y-shaped maze. We have previously identified using this method persistent spontaneous object recognition and temporal order memory deficits following mild-to-moderate TBI in the animals up to 35-day postinjury.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Aprendizagem em Labirinto , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Animais , Cognição , Transtornos Cognitivos/diagnóstico , Modelos Animais de Doenças , Masculino , Memória , Transtornos da Memória/diagnóstico , Ratos
12.
Lancet Psychiatry ; 6(11): 961-966, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31327707

RESUMO

Although mental disorders are a leading cause of disability in the Arab region, which includes 5·54% of the global population, Arab countries produce only 1·0% of the global output of peer-reviewed publications in mental health research. Various stakeholders, including Arab mental health researchers, institutional and funding agency officials, and international research collaborators, convened to identify challenges faced by Arab mental health researchers and propose an evidence-informed call for action. Challenges identified include prevalent stigma and low awareness, conflict and war, scarce institutional and funding resources, inadequate publishing opportunities, insufficient training in mental health research, and shortage of reliable and valid assessment tools. The proposed action plan includes ways of addressing stigma and spreading awareness, increasing collaborative efforts, building research infrastructure, strengthening the mental health workforce, and translating research findings into a call to action on societal and governmental levels. The proposed action plan could provide a roadmap for Arab mental health researchers and research institutions, which might ultimately increase research productivity in the Arab region and close the gap between Arab countries and the rest of the world.


Assuntos
Árabes , Transtornos Mentais , Pesquisa , Humanos , Saúde Mental , Oriente Médio
13.
BMC Neurosci ; 20(1): 8, 2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30832562

RESUMO

BACKGROUND: The electroencephalogram (EEG) is a widely used laboratory technique in rodent models of epilepsy, traumatic brain injury (TBI), and other neurological diseases accompanied by seizures. Obtaining prolonged continuous EEG tracings over weeks to months is essential to adequately answer research questions related to the chronobiology of seizure emergence, and to the effect of potential novel treatment strategies. Current EEG recording methods include wired and the more recent but very costly wireless technologies. Wired continuous long-term EEG in rodents remains the mainstay approach but is often technically challenging due to the notorious frequent EEG cable disconnections from the rodent's head, and to poor signal-to-noise ratio especially when simultaneously monitoring multiple animals. Premature EEG cable disconnections and cable movement-related artifacts result from the animal's natural mobility, and subsequent tension on the EEG wires, as well as from potential vigorous and frequent seizures. These challenges are often accompanied by injuries to the scalp, and result in early terminations of costly experiments. RESULTS: Here we describe an enhanced customized swivel-balance EEG-cage system that allows tension-free rat mobility. The cage setup markedly improves the safety and longevity of current existing wired continuous long-term EEG. Prevention of EEG cable detachments is further enhanced by a special attention to surgical electrode anchoring to the skull. In addition to mechanically preventing premature disconnections, the detailed stepwise approach to the electrical shielding, wiring and grounding required for artifact-free high signal-to-noise ratio recordings is also included. The successful application of our EEG cage system in various rat models of brain insults and epilepsy is described with illustrative high quality tracings of seizures and electrographic patterns obtained during continuous and simultaneous monitoring of multiple rats early and up to 3 months post-brain insult. CONCLUSION: Our simple-to-implement key modifications to the EEG cage setup allow the safe acquisition of substantial high quality wired EEG data without resorting to the still costly wireless technologies.


Assuntos
Eletroencefalografia/instrumentação , Modelos Animais , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Eletrodos Implantados , Epilepsia/fisiopatologia , Desenho de Equipamento , Abrigo para Animais , Masculino , Movimento , Ratos , Ratos Sprague-Dawley , Convulsões/fisiopatologia
14.
Epilepsy Behav ; 92: 332-340, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30769278

RESUMO

Hypoxic encephalopathy of the newborn is a major cause of long-term neurological sequelae. We have previously shown that CEP-701 (lestaurtinib), a drug with an established safety profile in children, attenuates short-term hyperexcitability and tropomyosin-related kinase B (TrkB) receptor activation in a well-established rat model of early life hypoxic seizures (HS). Here, we investigated the potential long-term neuroprotective effects of a post-HS transient CEP-701 treatment. Following exposure to global hypoxia, 10 day old male Sprague-Dawley pups received CEP-701 or its vehicle and were sequentially subjected to the light-dark box test (LDT), forced swim test (FST), open field test (OFT), Morris water maze (MWM), and the modified active avoidance (MAAV) test between postnatal days 24 and 44 (P24-44). Spontaneous seizure activity was assessed by epidural cortical electroencephalography (EEG) between P50 and 100. Neuronal density and glial fibrillary acidic protein (GFAP) levels were evaluated on histological sections in the hippocampus, amygdala, and prefrontal cortex at P100. Vehicle-treated hypoxic rats exhibited significantly increased immobility in the FST compared with controls, and post-HS CEP-701 administration reversed this HS-induced depressive-like behavior (p < 0.05). In the MAAV test, CEP-701-treated hypoxic rats were slower at learning both context-cued and tone-signaled shock-avoidance behaviors (p < 0.05). All other behavioral outcomes were comparable, and no recurrent seizures, neuronal loss, or increase in GFAP levels were detected in any of the groups. We showed that early life HS predispose to long-lasting depressive-like behaviors, and that these are prevented by CEP-701, likely via TrkB modulation. Future mechanistically more specific studies will further investigate the potential role of TrkB signaling pathway modulation in achieving neuroprotection against neonatal HS, without causing neurodevelopmental adverse effects.


Assuntos
Carbazóis/uso terapêutico , Cognição/efeitos dos fármacos , Emoções/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Convulsões/tratamento farmacológico , Animais , Animais Recém-Nascidos , Carbazóis/farmacologia , Cognição/fisiologia , Emoções/fisiologia , Hipóxia/complicações , Hipóxia/psicologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Convulsões/etiologia , Convulsões/psicologia
15.
Front Aging Neurosci ; 10: 277, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30279655

RESUMO

Background: Dementia secondary to neurodegenerative diseases is prevalent among older adults and leads to social, psychological and economic burden on patients, caregivers and the community as a whole. Cognitive reserve factors such as education, and mental stimulation among others were hypothesized to contribute to the resilience against age-related cognitive impairment. Educational attainment, occupation complexity, physical activity, and leisure activity are explored in the context of protecting the older adults' cognitive function. We investigated the cognitive reserve effect on dementia, cognitive decline and impairment, and global cognitive function. Methods: This study is a secondary analysis of data from a cross-sectional, community-based cohort study that aimed at investigating factors associated with dementia and their prevalence. The sample was of 508 community based older adults in Lebanon, aged 65 years and above in addition to 502 informants designated by these older adults. Older adults and informants answered structured questionnaires administered by interviewers, as well as a physical assessment and a neurological examination. Older adults were diagnosed for dementia. Global cognitive function, depression, and cognitive decline were assessed. Results: Older adults with dementia had lower levels of education, and attained lower occupational complexity. Factors such as high education, complex occupation attainment, and leisure activity, significantly predicted better global cognitive function. An older adult who attained high education levels or high complexity level occupation was 7.1 or 4.6 times more likely to have better global cognitive function than another who attained lower education or complexity level occupation respectively. Conclusion: These results suggest that cognitive reserve factors ought to be taken into consideration clinically during the course of dementia diagnosis and when initiating community-based preventive strategies.

16.
Clin Neuropsychol ; 32(sup1): 102-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29893187

RESUMO

OBJECTIVE: This study aimed to provide normative data for four trials of the Rey figure Test - a complex design used to assess visuoconstructional abilities, aspects of visual memory, and aspects of executive functioning. Despite its frequent clinical and research use in the Arab region, published studies regarding the measures' adaptation or normative data remain absent. METHOD: We administered the Rey figure on a convenience sample of Lebanese (n = 254) aged 30 years to 99. RESULTS: We examined the impact of relevant demographics, and found that age, gender, and years of education impacted scores, and norms were derived based on these variables. Such normative data for the Rey figure enhance its practicality and psychometric adequacy for use in research and clinical settings in Lebanon.


Assuntos
Testes Neuropsicológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Função Executiva , Feminino , Humanos , Idioma , Líbano , Masculino , Memória , Pessoa de Meia-Idade , Psicometria , Valores de Referência , Reprodutibilidade dos Testes
17.
Behav Brain Res ; 340: 1-13, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29126932

RESUMO

Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior treatment with DHA may be a desirable strategy to improve the therapeutic efficacy of NSC transplantation in TBI.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/cirurgia , Ácidos Docosa-Hexaenoicos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/transplante , Fármacos Neuroprotetores/farmacologia , Animais , Animais Recém-Nascidos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Encéfalo/cirurgia , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Células Cultivadas , Terapia Combinada , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Neurônios Dopaminérgicos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Células-Tronco Neurais/patologia , Células-Tronco Neurais/fisiologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Neuroglia/fisiologia , Distribuição Aleatória , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Nicho de Células-Tronco , Transplante de Células-Tronco/métodos
18.
Behav Brain Res ; 340: 49-62, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28043902

RESUMO

TBI is a nondegenerative, noncongenital insult to the brain from an external mechanical force; for instance a violent blow in a car accident. It is a complex injury with a broad spectrum of symptoms and has become a major cause of death and disability in addition to being a burden on public health and societies worldwide. As such, finding a therapy for TBI has become a major health concern for many countries, which has led to the emergence of many monotherapies that have shown promising effects in animal models of TBI, but have not yet proven any significant efficacy in clinical trials. In this paper, we will review existing and novel TBI treatment options. We will first shed light on the complex pathophysiology and molecular mechanisms of this disorder, understanding of which is a necessity for launching any treatment option. We will then review most of the currently available treatments for TBI including the recent approaches in the field of stem cell therapy as an optimal solution to treat TBI. Therapy using endogenous stem cells will be reviewed, followed by therapies utilizing exogenous stem cells from embryonic, induced pluripotent, mesenchymal, and neural origin. Combination therapy is also discussed as an emergent novel approach to treat TBI. Two approaches are highlighted, an approach concerning growth factors and another using ROCK inhibitors. These approaches are highlighted with regard to their benefits in minimizing the outcomes of TBI. Finally, we focus on the consequent improvements in motor and cognitive functions after stem cell therapy. Overall, this review will cover existing treatment options and recent advancements in TBI therapy, with a focus on the potential application of these strategies as a solution to improve the functional outcomes of TBI.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Terapia Combinada , Transplante de Células-Tronco , Animais , Lesões Encefálicas Traumáticas/fisiopatologia , Terapia Combinada/métodos , Humanos , Transplante de Células-Tronco/métodos
19.
Sci Rep ; 7: 45926, 2017 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-28374837

RESUMO

Multiple Sclerosis is associated with deficient serum 25 hydroxyvitamin D (25 (OH)D) level and cognitive impairment. The aim of this study is to evaluate cognitive performance in MS patients with deficient 25 (OH)D (<25 ng/ml) compared to patients with sufficient levels (>35 ng/ml), then to evaluate the change in cognitive performance after 3 months of vitamin D3 oral replacement. Eighty-eight MS patients with relapsing remitting and clinically isolated type of MS, older than 18 years treated with interferon beta were enrolled. Cognitive testing was performed at baseline and at 3 months using the Montreal Cognitive Assessment (MoCA), Stroop, Symbol Digit Modalities (SDMT) and Brief Visuospatial Memory Test (BVMT-R). Serum 25 (OH)D was measured at baseline and at the end of the study. Vitamin D3 replacement improved the MS patients' cognitive performance after 3 months on the MoCA and BVMT-Delayed Recall (DR). Sufficient serum 25 (OH)D level predicted better cognitive performance on the BVMT-DR at baseline (ß: 1.74, p: <0.008) and 3 months (ß: 1.93, p: <0.01) after adjusting for all measured confounding variables. Vitamin D3 replacement could improve cognitive performance in MS patients and make a significant difference in the patient's quality of life.


Assuntos
Colecalciferol/uso terapêutico , Cognição/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Deficiência de Vitamina D/tratamento farmacológico , Adulto , Calcifediol/sangue , Colecalciferol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/psicologia , Análise Multivariada , Testes Neuropsicológicos , Estudos Prospectivos , Qualidade de Vida , Deficiência de Vitamina D/complicações , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico , Adulto Jovem
20.
Medicine (Baltimore) ; 95(47): e5342, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27893670

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a debilitating medical and emerging public health problem that is affecting people worldwide due to a multitude of factors including both domestic and war-related acts. The objective of this paper is to systematically review the status of TBI in Lebanon - a Middle Eastern country with a weak health system that was chartered by several wars and intermittent outbursts of violence - in order to identify the present gaps in knowledge, direct future research initiatives and to assist policy makers in planning progressive and rehabilitative policies. METHODS: OVID/Medline, PubMed, Scopus databases and Google Scholar were lastly searched on April 15, 2016 to identify all published research studies on TBI in Lebanon. Studies published in English, Arabic or French that assessed Lebanese patients afflicted by TBI in Lebanon were warranting inclusion in this review. Case reports, reviews, biographies and abstracts were excluded. Throughout the whole review process, reviewers worked independently and in duplicate during study selection, data abstraction and methodological assessment using the Downs and Black Checklist. RESULTS: In total, 11 studies were recognized eligible as they assessed Lebanese patients afflicted by TBI on Lebanese soils. Considerable methodological variation was found among the identified studies. All studies, except for two that evaluated domestic causes such as falls, reported TBI due to war-related injuries. Age distribution of TBI victims revealed two peaks, young adults between 18 and 40 years, and older adults aged 60 years and above, where males constituted the majority. Only three studies reported rates of mild TBI. Mortality, rehabilitation and systemic injury rates were rarely reported and so were the complications involved; infections were an exception. CONCLUSION: Apparently, status of TBI in Lebanon suffers from several gaps which need to be bridged through implementing more basic, epidemiological, clinical and translational research in this field in the future.


Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Disparidades em Assistência à Saúde , Humanos , Líbano/epidemiologia
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