Current Pharmaceutical Design - Volume 22, Issue 6, 2016
Volume 22, Issue 6, 2016
-
-
The Yin and Yang of Antiviral Innate Immunity in Central Nervous System
The innate immune system provides protection against invading neurotropic viruses. It acts as the first line of defense against invading viruses and plays an elementary role in their pathogenesis. The list of viruses capable of infecting human central nervous system (CNS) is quite long, most important of them are Japanese Encephalitis virus (JEV), rabies virus, West Nile virus (WNV), herpes simplex virus (HSV), St. Louis encephalitis virus (SLEV), La Crosse virus, tick borne encephalitis virus (TEBE) and polio virus. Germ line pattern recognition receptors (PRRs) such as Toll like receptors (TLRs), nucleotide binding oligomerization domain (NOD) - like receptors (NLRs), retinoic acid-inducible gene I (RIG-I) -like helicases or RIG-I-like receptors (RLRs) and cytosolic DNA sensors recognize the pathogen associated molecular patterns (PAMPs) and initiate an immune response against invading pathogen. Although PRRs were originally characterized in peripheral immune cells but accumulating evidence also suggest their crucial roles in CNS to combat against neurotropic viruses. In this review, we will highlight the recent developments in our understating of the mechanisms by which PRRs in resident brain cells provide protection against invading neurotropic viruses.
-
-
-
Oligodendrocyte Development and Myelination in Neurodevelopment: Molecular Mechanisms in Health and Disease
Authors: Andreia Barateiro, Dora Brites and Adelaide FernandesOligodendrocytes are the myelinating cells of the central nervous system that constitute about 5 to 10% of the total glial population. These cells are responsible for myelin sheath production, which is essential not only for the rapid and efficient conduction of the electrical impulses along the axons, but also for preserving axonal integrity. Oligodendrocytes arise from oligodendrocyte progenitor cells that proliferate and differentiate just before and after birth, under a highly-regulated program. Both oligodendrocytes and their precursors are very susceptible to injury by several mechanisms, including excitotoxic damage, oxidative stress and inflammatory events. In this review, we will cover not only several important aspects of oligodendrocyte development and regulatory mechanisms involved in this process, but also some of the most important pathways of injury associated to oligodendrogenesis. Moreover, we will also address some neurological disorders along life journey that present impairment in oligodendrocyte function and in myelination during neurodevelopment, such as periventricular leukomalacia, hypoxia/ischemia and hyperbilirubinemia that in turn can potentiate the emergence of neurological and neurodegenerative diseases like schizophrenia, multiple sclerosis and Alzheimer’s disease.
-
-
-
Biomarkers in Silent Traumatic Brain Injury
Authors: Constantine N. Antonopoulos and Nikolaos P.E. KadoglouTraumatic brain injury (TBI) has been recognized among the leading causes of mortality and morbidity in young adults. Traditionally, the diagnosis of TBI has been based on neuroimaging. However, a significant portion of insulted patients appear to be apparently asymptomatic. As a result, more elaborate indices of silent TBI are required in order to immediately detect focal and diffuse asymptomatic TBI. Such valid indices will potentially increase the efficacy of therapeutic strategies in TBI patients. In this review of the literature, we present novel circulating biomolecules, as potential biomarkers of silent TBI, like neurofilaments, Cleaved-Tau (C-Tau), Microtubule-Associated Protein 2 (MAP2), Neuron-Specific Enolase, S100B and ferritin. In addition to this, assessment of white matter abnormalities and white matter integrity by diffusion tensor imaging (DTI) have emerged as promising sensitive neuroimaging methods of silent TBI. An integrated research is needed to fully understand the interplay between all the aforementioned indices and DTI. The potential diagnostic, therapeutic and prognostic values of the all aforementioned indices will be analyzed in the proposed review.
-
-
-
Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer’s Disease
Authors: Ligia J. Dominguez and Mario BarbagalloAge-associated cognitive decline and dementia are conditions in which there is deterioration in memory, thinking, and behavior, with profound effects on the ability to perform everyday activities and well-being. Even if dementia mainly affects older persons, it is not a normal part of aging. Alzheimer's disease accounts for 60–75% of dementia cases. The number of persons affected will increase in the next decades in parallel with aging of the world population. Hence, unless some approach is found to reduce age-related deterioration of cognitive functions, health care costs will continue to rise exponentially. There is a wealth of epidemiological evidence supporting a relationship between diet and Alzheimer's disease, and suggesting that the risk of cognitive decline may be reduced by dietary interventions. It has been proposed that adopting a healthy diet and lifestyle that improves cardiovascular function may help delaying the onset of Alzheimer's disease due to its potential association with vascular disease. Several nutrients, dietary components, supplements and dietary patterns have been reported in relation to their association with cognition and with the development of cognitive decline and Alzheimer’s disease. The possible effect of diet on the prevention of dementia is of tremendous scientific and general interest, because hitherto there is no definitive evidence of any effective pharmacological treatment for dementia. The aim of this review is to evaluate the evidence for the effects of some dietary components, supplements, and dietary patterns as neuroprotective, with potential to delay cognitive decline and the onset of dementia.
-
-
-
Role of Immune Cells in the Course of Central Nervous System Injury: Modulation with Natural Products
Authors: Thea Magrone, Matteo A. Russo and Emilio JirilloImmune cells actively participate to the central nervous system (CNS) injury either damaging or protecting neural tissue with release of various mediators. Residential microglia and monocyte-derived macrophages play a fundamental role within the injured CNS and, here, special emphasis will be placed on M1 and M2 macrophages for their different functional activities. On the other hand, peripheral T regulatory (Treg) cells exert antiinflammatory activities in the diseased host. In this respect, activation of Treg cells by nutraceuticals may represent a novel approach to treat neuroinflammation. Omega-3 fatty acids and polyphenols will be described as substances endowed with antioxidant and anti-inflammatory activities. However, taking into account that Treg cells act in the later phase of CNS injury, favoring immune suppression, manipulation of host immune system with both substances requires caution to avoid undesired side effects.
-
-
-
The Role of Chinese Herbs and Acupuncture on the Inflammation Reaction After Cerebral Ischemia
Authors: Feng Wan, Xin Niu, Yi-Lun Song and Yin-Chu SiAs a complex pathological process, immune inflammatory reaction plays an important role in the injury by cerebral ischemia. Inflammatory mediators can promote each other to coregulate the immune inflammatory reaction. Inflammatory cytokines play a pivotal role in regulating the immune inflammatory reaction process. Chinese herbs and acupuncture can exert a protective effect against neuronal damage by cerebral ischemia by inhibiting the production and expression of inflammatory cytokines and adhesion molecules, effectively blocking the inflammatory reaction and reducing the apoptosis of nerve cells.
-
-
-
Non Pharmacological Strategies to Promote Spinal Cord Regeneration: A View on Some Individual or Combined Approaches
Authors: Ivis-Ibrahim Morales, Diana Toscano-Tejeida and Antonio IbarraSpinal cord injury (SCI) is a complex condition that can result in functional impairment and paralysis, and occurs more frequently in young men. Several studies tested diverse treatments; however none achieved effective neuronal regeneration or improvement in neural function. Current research is being performed in areas such as cellular therapy (Schwann cells, embryonic stem cells, pluripotent stem cells, mesenchymal stem cells and olfactory cells), growth factors (BDNF), inhibitory molecules, fibroglial scar, gene therapies, etc. Some strategies have provided encouraging results by themselves, others have been tested as a combination, showing an improved outcome after SCI. Combined strategies could be more effective than individual therapies; for instance, cotransplantation of cells at the injury site to maximize their effect has been used, and it has demonstrated a greater efficacy in comparison to grafts of stem cells or of a particular cell type. The combination of neurotrophic factors such as BDNF and NT- 3 enhances axonal regeneration and myelination; other therapies include the use of biological matrices in combination with inhibitors of glial scar formation. Chondroitinase ABC (ChABC) has shown synergistic effects with other strategies, specifically to improve regeneration and functional recovery after SCI. Experimental evidence suggests that it is possible to obtain better results with a combination of strategies, which justifies further research for therapeutic approaches. This review intends to compile the most relevant information about available up-to-date therapeutic strategies that are administered alone or in combination with others, and have offered the best results in neural regeneration after spinal cord injury.
-
-
-
Experimental and Clinical Advances in Immunotherapy Strategies for Spinal Cord Injury Target on MAIs and Their Receptors
Authors: Xiu-Min Lu, Jing-Xiang Wei, Lan Xiao, Ya-Hai Shu and Yong-Tang WangIn the injured adult mammalian central nervous system (CNS), the failure of axonal regeneration is thought to be attributed, at least in part, to various myelin-associated inhibitors (MAIs), such as Nogo, myelinassociated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp) around the damaged site. Interestingly, these three structurally different inhibitors share two common receptors, Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB), and transduce the inhibitory signal into neurons via their complex combinant and co-receptors, such as p75 neurotrophin receptor (p75NTR), Nogo receptor-interacting protein 1 (LINGO-1), and TROY. Accordingly, targeting of the whole myelin or just portions by immunization has been proved to be neuroprotective and is able to promote regeneration in the injured spinal cords. In the past few years, vaccine approaches were initially achieved and could induce the production of antibodies against inhibitors in myelin to block the inhibitory effects and promote functional recovery in spinal cord injury (SCI) models by immunizing with MAIs, such as purified myelin, spinal cord homogenates, or their receptors with the concept of protective autoimmunity formulated. However, for safety consideration, further work is necessary before the immunotherapy strategies can be adopted to treat human injured spinal cords.
-
-
-
Evolving Insights into the Pathophysiology of Diabetic Neuropathy: Implications of Malfunctioning Glia and Discovery of Novel Therapeutic Targets
Authors: Md Habibur Rahman, Mithilesh Kumar Jha and Kyoungho SukDiabetic neuropathy subsequent to chronic high blood glucose-induced nerve damage is one of the most frustrating and debilitating complications of diabetes, which affects the quality of life in patients with diabetes. Approximately 60–70% of patients with diabetes suffer from a distal symmetrical form of mild to severe neuropathy that progresses in a fiber-length-dependent pattern, with sensory and autonomic manifestations predominating. High glucose and oxidative stress-mediated damage in neurons and glial cells, as well as neuroinflammation and crosstalk between these disease processes, have garnered immense attention as the essential mechanisms underlying the development and progression of diabetic neuropathy. Although the metabolic causes of diabetic neuropathy are well understood and documented, treatment options for this disorder are still limited, highlighting the need for further studies to identify new molecular and therapeutic targets. This review covers recent advances in our knowledge of the pathophysiology of diabetic neuropathy, discusses how persistent hyperglycemic conditions and malfunctioning glia drive disease progression, and finally explores the possibilities and challenges offered by several potential novel therapeutic targets for both preventing and reversing diabetic neuropathy.
-
-
-
Combined Treatment Fkt-Botulinum Toxin Type A (Btx-A) in Patients with Strumpell-Lorrain Disease
The Hereditary Spastic Paraparesis (HSP) or Strumpell-Lorrain disease is a heterogeneous neurodegenerative disease of the spinal cord. It is genetically transmitted and characterized by a progressive muscle weakness, spasticity of the lower limbs and awkward gain. There is no specific pharmacological treatment. The pharmacological therapy decreases the muscle tone and prevents stiffening). Physiotherapy restrains the progression of muscle atrophy, delays contraction of the tendons and gives greater mobility to people affected by the disease. The aim of this study is to demonstrate the efficacy of the combined treatment Fkt and Btx-A in patients with HSP. Retrospective study was conducted recruiting ten patients with spasticity according to Asworth modified scale of at least 2 and with gait deficit. They received treatment for 5 years with incobotulinumtoxinA and physiokinesiotherapy for addressing spasticity in the lower limbs. We evaluated muscle tone with miometric measurement both at the first visit (T0), and at subsequent ones (T1 after 30 days, T2 after 3 months from the first infiltration, T3 after 4 months up to the date of the following infiltration, T4 after 5 months). Baropodometric examination has proven essential for the study of the distribution of loads in statics and dynamics. The data analysis regarding tone assessment through measurements with Myoton highlighted hypertonus reduction in all the three muscle groups examined at T1 and the maintenance of constant values up to 5 months after the first infiltration. It also showed an increase in the percentage of back foot loading in both feet up to T4 (new inoculation, p<0, 05%). Baropodometric examination in dynamics (in particular the speed of the step) showed a gradual increase in this parameter which reaches a peak at 5 months (p<0, 05%) and then declines again in conjunction with the next infiltration treatment. This study showed the benefit of combined treatment with Btx and Fkt. The use of a local muscle relaxant drug with a physical targeted exercise guarantees better mobility of the treated segments, reducing tendon retractions as much as possible, and guarantees an adequate postural alignment. Baropodometric examination highlights a more advantageous distribution load, quite essential for avoiding tendinitis due to overload. Our data observation in the 5 years study shows how the curve relative to the speed of step and the graphics related to the variations of muscle tone remain almost constant with detectable improvement.
-
Volumes & issues
-
Volume 31 (2025)
-
Volume (2025)
-
Volume 30 (2024)
-
Volume 29 (2023)
-
Volume 28 (2022)
-
Volume 27 (2021)
-
Volume 26 (2020)
-
Volume 25 (2019)
-
Volume 24 (2018)
-
Volume 23 (2017)
-
Volume 22 (2016)
-
Volume 21 (2015)
-
Volume 20 (2014)
-
Volume 19 (2013)
-
Volume 18 (2012)
-
Volume 17 (2011)
-
Volume 16 (2010)
-
Volume 15 (2009)
-
Volume 14 (2008)
-
Volume 13 (2007)
-
Volume 12 (2006)
-
Volume 11 (2005)
-
Volume 10 (2004)
-
Volume 9 (2003)
-
Volume 8 (2002)
-
Volume 7 (2001)
-
Volume 6 (2000)
Most Read This Month
