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Microglia are the brain resident immune cells; they can produce a large variety of growth factors (GFs) to prevent neuronal damages and promote recovery. In neurodegenerative diseases, microglia can play both benefic and deleterious roles, depending on different factors and disease context. In multiple sclerosis, microglia are involved in both demyelination (DM) and remyelination (RM) processes. Recent studies suggest a beneficial role of microglia in regenerative processes. These include the regenerative development of myelin after DM. This review gives an overlook of how microglia and GFs can influence the RM properties.

Microglia are the brain resident immune cells; they can produce a large variety of growth factors (GFs) to prevent neuronal damages and promote recovery. In neurodegenerative diseases, microglia can play both benefic and deleterious roles, depending on different factors and disease context. In multiple sclerosis, microglia are involved in both demyelination (DM) and remyelination (RM) processes. Recent studies suggest a beneficial role of microglia in regenerative processes. These include the regenerative development of myelin after DM. This review gives an overlook of how microglia and GFs can influence the RM properties. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether aerobic capacity explains the level of self-reported physical activity, physical functioning, and participation and autonomy in daily living in persons with multiple sclerosis-related fatigue. Design: A cross-sectional study. Patients: Sixty-two participants with multiple sclerosis-related fatigue. Methods: Aerobic capacity was measured with a leg ergometer and was expressed as maximal oxygen uptake (VO2max, in ml/kg/min). Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities (PASIPD), physical functioning with the Short Form 36 – physical functioning (SF36-pf), and participation and autonomy in daily living with the Impact on Participation and Autonomy questionnaire (IPA). Multiple regression analyses were performed, adjusted for potential confounders (gender, age, body mass index, educational level, and employment status). Results: Mean maximal oxygen uptake (VO2max) was 23.9 ml/kg/min (standard deviation (SD) 6.3 ml/kg/min). There was no significant relationship between VO2max and physical activity (PASIPD): β = 0.320, 95% confidence interval (95% CI) = –0.109 to 0.749, R2 = 10.8%. Higher VO2max correlated with better physical functioning (SF36-pf): β = 1.527, 95% CI = 0.820–2.234, R2 = 25.9%, and was significantly related to IPA domains “autonomy indoors” (β = –0.043, 95% CI = –0.067 to –0.020, R2 = 20.6%), “autonomy outdoors” (β = –0.037, 95% CI = –0.062 to –0.012, R2 = 18.2%) and “social life and relationships” (β=–0.033, 95% CI = –0.060 to –0.007, R2 = 21.3%). Conclusion: Maximum aerobic capacity was severely reduced in persons with multiple sclerosis-related fatigue. This partly explains the limited physical functioning and restrictions in participation and autonomy indoors, outdoors and in social life and relationships in these persons.

Multiplesclerosis (MS) is an immunemediatedchronicinflammatorydiseasecharacterizedbyneuroinflammationandneurodegeneration of thecentralnervoussystem (CNS). Thecourseandtreatment of thediseasearethemostcommonquestionsaskedbypatientswith MS. Questionsconcerningtherelationship of MS withpregnancyandthepostpartumperiod, assistedreproductiontechnology, preand post-operativeproblemsandvaccinesarealsofrequentlyasked, andsome of theanswersarestillcontroversial. It is knownthat MS has noharmfuleffect on pregnancyorthefetus. The presence of MS is not an indicationtoterminatepregnancy, anddiseaseprogression is not foundto be relatedwithpregnancy. Therelapsesduringpregnancyareknowntohave a mildcourse but on thecontrary, therelapsesduringthepostpartumperiodtendto be particularly severe. It is suggestedto stop takingdiseasemodifyingtherapies (DMT) at leastonemonthpriortothepregnancyplanningperiod. There is nocontraindicationfortheuseof conventionalcontraceptives; however it is knownthat oral contraceptivesincreasethe risk of venousthromboembolism in MS patientswithimpairedmobility. Patientswithdecreasedfertilityandwhoarecandidatesforassistedreproductiontechnologies (ART) should be informedabouttheincreased risk of relapse. It is alsoshownthatproceduresunderspinalanesthesiaincreasethe risk of relapse, so general anesthesiamay be an alternative in MS patients. Cautioustitration of anestheticdrugs, continuousmonitoringandusingthelowestpossibleeffectivedosearethetreatmentprinciples. Exceptforhepatitis B therearenoadequatepublished data aboutvaccinesthatcause CNS demyelination. Inthispaper, wediscuss how toapproachtheabovementionedparticularissues in MS patients

OBJECTIVE: Multiple Sclerosis (MS) is such a disease that not only leads to different levels of disabilities in mobility and functional activities, but also creates severe disability and impairs the quality of life via causing limitations in person’s social and occupational life. Most MS patients experience depression. Besides, cognitive dysfunction is present. In this study, it is aimed to detect the frequency of depression and cognitive dysfunction in MS patients. METHODS: 108 patients diagnosed with MS are evaluated. Each one of the MS patients are administered the Brief Repeatable Battery of Neuropsychological Test (10/36 Spatial Recall Test, Symbol Digit Modalities Test, Paced Auditory Serial Test, Word List Generation Test), Beck Depression Inventory and Benedict Test. RESULTS: Of the 108 MS cases participated in the study, 69.4 % (n=75) are female, while 30.6 % (n=33) are male patients. Depression is detected in 19.5 % (n=21) of the patients, while cognitive dysfunction is detected in 41.7 % (n=45). Depression and cognitive dysfunction are detected together in 13.9 % (n=15) of the patients. CONCLUSION: Depression and cognitive dysfunction are not a rarity in patients with MS. A multidisciplinary approach is needed to treat the patients diagnosed with MS

Aspirin is widely used to lessen the risks of cardiovascular events. Some studies suggest that patients with multiple sclerosis have an increased risk for some cardiovascular events, for example, venous thromboembolism and perhaps ischemic strokes, raising the possibility that aspirin could lessen these increased risks in this population or subgroups (patients with limited mobility and/or antiphospholipid antibodies). However, aspirin causes a small increased risk of hemorrhagic stroke, which is a concern as it could potentially worsen a compromised blood-brain barrier. Aspirin has the potential to ameliorate the disease process in multiple sclerosis (for example, by limiting some components of inflammation), but aspirin also has the potential to inhibit mitochondrial complex I activity, which is already reduced in multiple sclerosis. In an experimental setting of a cerebral ischemic lesion, aspirin promoted the proliferation and/or differentiation of oligodendrocyte precursors, raising the possibility that aspirin could facilitate remyelination efforts in multiple sclerosis. Other actions by aspirin may lead to small improvements of some symptoms (for example, lessening fatigue). Here we consider potential benefits and risks of aspirin usage by patients with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Malnutrition is common in neurodegenerative disorders and is associated with a worse prognosis and an increased risk of complications. Factors leading to malnutrition in these patients are: diseased nutrient intake, due to anorexia, dysphagia and other factors, gastrointestinal symptoms, and energy expenditure alterations. Nutritional evaluation and monitoring is mandatory and should be part of regular clinical evaluation. It will help to identify those patients that need specialized nutritional support. In this paper, relevant aspects regarding nutritional evaluation and support in patients suffering from a neurodegenerative disorder are reviewed, including amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease and dementia. [ABSTRACT FROM AUTHOR]

Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2"enzymes. As a result of our efforts to develop these compounds as therapeutics for brain health, we have formulated two innovative criteria for drug development: the first concept is the use of pro-electrophilic drugs (PEDs) that are innocuous in and of themselves; and the second concept involves the use of compounds that are pathologically activated therapeutics (PATs); i.e., these small molecules are chemically converted to their active form by the very oxidative stress that they are designed to then combat. The chemical basis for PED and PAT drugs is embodied in the ortho- and para-hydroquinone electrophilic cores of the molecules, which are oxidized by the Cu(2+)/Cu(+) cycling system (or potentially by other transition metals). Importantly, this cycling pathway is under stringent regulation by the cell redox state. We propose that redox-dependent quinone formation is the predominant mechanism for formation of PED and PAT drugs from their precursor compounds. In fact, redox-dependent generation of the active form of drug from the "pro-form" distinguishes this therapeutic approach from traditional EPs such as curcumin, and results in a decrease in clinical side effects at therapeutic concentrations, e.g., lack of reaction with other thiols such as glutathione (GSH), which can result in lowering GSH and inducing oxidative stress in normal cells. We consider this pro-drug quality of PED/PAT compounds to be a key factor for generating drugs to be used to combat neurodegenerative diseases that will be clinically tolerated. Given the contribution of oxidative stress to the pathology of multiple neurodegenerative diseases, the Keap1/Nrf2/ARE pathway represents a promising drug target for these PED/PAT agents., (© 2013 Published by Elsevier Inc.)

Living cells maintain a balance between oxidation and reduction, and perturbations of this redox balance are thought to contribute to various diseases. Recent attempts to regulate redox state have focused on electrophiles (EPs), which activate potent cellular defense systems against oxidative stress. One example of this approach is exemplified by carnosic acid (CA) and carnosol (CS), compounds that are found in the herb rosemary (Rosmarinus officinalis). Importantly, CA and CS themselves are not electrophilic, but in response to oxidation, become electrophilic, and then activate the Keap1/Nrf2/ARE (antioxidant-response element) transcription pathway to synthesize endogenous antioxidant "phase 2" enzymes. As a result of our efforts to develop these compounds as therapeutics for brain health, we have formulated two innovative criteria for drug development: the first concept is the use of pro-electrophilic drugs (PEDs) that are innocuous in and of themselves; and the second concept involves the use of compounds that are pathologically activated therapeutics (PATs);i.e., these small molecules are chemically converted to their active form by the very oxidative stress that they are designed to then combat. The chemical basis for PED and PAT drugs is embodied in the ortho- and para-hydroquinone electrophilic cores of the molecules, which are oxidized by the Cu(2+)/Cu(+) cycling system (or potentially by other transition metals). Importantly, this cycling pathway is under stringent regulation by the cell redox state. We propose that redox-dependent quinone formation is the predominant mechanism for formation of PED and PAT drugs from their precursor compounds. In fact, redox-dependent generation of the active form of drug from the "pro-form" distinguishes this therapeutic approach from traditional EPs such as curcumin, and results in a decrease in clinical side effects at therapeutic concentrations, e.g., lack of reaction with other thiols such as glutathione (GSH), which can result in lowering GSH and inducing oxidative stress in normal cells. We consider this pro-drug quality of PED/PAT compoundsto be a key factor for generating drugs to be used to combat neurodegenerative diseases that will be clinically tolerated. Given the contribution of oxidative stress to the pathology of multiple neurodegenerative diseases, the Keap1/Nrf2/ARE pathway represents a promising drug target for these PED/PAT agents., (© 2013 Published by Elsevier Inc.)