Loading...

Table of Content

    07 December 2015, Volume 10 Issue 11 Previous Issue    Next Issue
    For Selected: Toggle Thumbnails
    Use of sensory substitution devices as a model system for investigating cross-modal neuroplasticity in humans
    Amy C. Nau, Matthew C. Murphy, Kevin C. Chan
    2015, 10 (11):  1717-1719.  doi: 10.4103/1673-5374.169612
    Abstract ( 168 )   PDF (378KB) ( 669 )   Save

    Blindness provides an unparalleled opportunity to study plasticity of the nervous system in humans. Seminal work in this area examined the often dramatic modifications to the visual cortex that result when visual input is completely absent from birth or very early in life. Our lab and others have demonstrated that decreases in visual pathway integrity occur in those with acquired blindness. More recent studies have begun to examine the changes occurring with certain disease states: patients suffering from optic neuritis secondary to multiple sclerosis and glaucoma, all so far demonstrate deterioration of the white matter tract architecture as a function of disease severity. This leads to the conclusion that the visual system as a whole is profoundly susceptible to degeneration even with small amounts of vision loss. On the surface, these investigations appear to have dire implications for vision restoration efforts. Yet, parallel studies which examine the phenomenon of cross-modal plasticity suggest that a remodeling of the central nervous system is possible, such that areas of the brain which have been deprived of normal afferent input are able to reconstitute themselves to be receptive to alternative sensory channels. The literature is rife with examples of investigations which show that the visual cortex will react to tactile and auditory stimuli in the blind but will be less readily recruited in sighted patients. Moreover, cross-modal interactions have been demonstrated well beyond the traditional “critical period” and into late adulthood, albeit perhaps in a less robust fashion. The notion that the adult brain is still capable of significant structural and functional remodeling after vision loss remains a beacon of hope for researchers and patients alike who dream of recovering vision through mechanical or biological means.

    Related Articles | Metrics
    Studying neurological disorders using induced pluripotent stem cells and optogenetics
    Eunice W.M. Chin, Eyleen L.K. Goh
    2015, 10 (11):  1720-1722.  doi: 10.4103/1673-5374.169607
    Abstract ( 221 )   PDF (349KB) ( 574 )   Save

    Neurological disorders are amongst the most widely studied human aliments. Yet, they are also one of the most poorly understood. An important role for genotype in the etiology of neurological disorders is suggested, even though most of these disorders are polygenic. For example, in schizophrenia and autism spectrum disorders, there is a 40–60 % concordance rate in monozygotic twins, with 60–90 % heritability. However, the mechanisms by which multiple genes and the genomic variations influence the phenotypes of the disorders remain to be understood. The complexities of the disorders are further compounded by the individual rarity of the genomic variations and their variable penetrance. Thus, conventional disease modeling that makes use of genome editing techniques to attain the desired disease genotype may not be the most suitable platform for tackling most neurological disorders. With the advent of induced pluripotent stem cell (iPSC) technology, there presents a revolutionizing method for modeling complex human disorders. iPSCs are somatic cells that can be reprogrammed through the use of transcription factors to restore pluripotency. Directed differentiation is one of the ultimate goals for iPSC technology. The differentiated cells obtained from iPSCs can be used for transplantation to replace lost cells, for drug screening, or to model patient-specific disease mechanisms in vitro. For neuroscience research, human iPSC-derived neurons make an ideal model system for the study of neurological disorders and the development of neural functionality and plasticity. In the event of neurodegeneration, they can act as a therapeutically relevant source of cells for replacement purposes.

    Related Articles | Metrics
    Efficacy of glucagon-like peptide-1 mimetics for neural regeneration
    Kazunori Sango*, Kazunori Utsunomiya
    2015, 10 (11):  1723-1724.  doi: 10.4103/1673-5374.169611
    Abstract ( 231 )   PDF (262KB) ( 653 )   Save

    Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L cells in response to nutrient ingestion and exhibits insulinotropic properties by stimulating specific G protein-linked receptors (GLP-1Rs) on pancreatic β cells. Several GLP-1 mimetics, such as exenatide (exendin-4 (Ex-4)), liraglutide, and lixisenatide, have been developed and approved as treatments for patients with type 2 diabetes. These peptides show bioactivities almost identical to those of GLP-1 and have a substantially longer plasma half-lifethan GLP-1 because of their resistance to dipeptidyl peptidase-4, a GLP-1 degrading enzyme. GLP-1Rs are found in not only the pancreas but also the extrapancreatic tissues, including the nervous tissues. It is important to note that GLP-1 mimetics can cross the blood brain barrier and directly act on neurons in the central nervous system. In addition to the inhibition of appetite, the neuroprotective properties of GLP-1 have been receiving increasing attention. Recent studies have suggested that GLP-1 mimetics confer beneficial effects in neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease, amyotrophic lateral sclerosis, ischemia and stroke, and multiple sclerosis. In particular, the neuroprotective properties of Ex-4 have been demonstrated inanimal and cell culture models of PD. A single-blinded clinical trial with 45 PD patients revealed that the treatment with Ex-4 significantly improved the cognition and memory of patients. The beneficial effects of GLP-1 mimetics on the peripheral nervous system (PNS) have also been reported. Both GLP-1 and Ex-4 delivered via osmotic minipumps prevented axonal degeneration in a rat model of pyridoxine-induced neuropathy. Treatment of streptozotocin (STZ)-induced diabetic mice with Ex-4 for 4 weeks restored reduced motor and sensory nerve conduction velocities and hypoalgesia without normalizing blood glucose levels. In addition, repeated intraperitoneal injections of Ex-4 significantly promoted axonal regeneration and functional recovery following sciatic nerve crush injury of normal adult rats. These findings are in agreement with in vitro studies that revealed that GLP-1 and Ex-4 promoted neurite outgrowth of rat pheochromocytoma-derived PC12 cells and adult mouse dorsal root ganglion (DRG) neurons. Together these results provide further evidence of the direct actions of Ex-4 on the PNS; however, the underlying mechanisms remain unclear. Our study aimed to elucidate the precise localization of GLP-1R in adult rat DRG in vivo and in vitro as well as determine the neurotrophic and neuroprotective properties of Ex-4 in adult rat DRG neurons.

    Related Articles | Metrics
    VEGF in the nervous system: an important target for research in neurodevelopmental and regenerative medicine
    Matthias Dumpich, Carsten Theiss
    2015, 10 (11):  1725-1726.  doi: 10.4103/1673-5374.170287
    Abstract ( 191 )   PDF (597KB) ( 595 )   Save

    VEGF is highly involved in axonal growth, neurodevelopment and in the pathogenesis of different neurological disorders. It enhances neuroprotection under unfavorable conditions and supports the growth of cerebral tumor tissue. VEGF’s effects in axon guidance are primarily mediated via reorganization of the actin cytoskeleton, but the exact downstream signaling of VEGF-signaling is not clear yet. All of those aspects lead us to suspect that VEGF will play a big role in upcoming neurological investigations and clinical treatments. It is conceivable that stimulation of axonal growth via VEGF will be used to support rehabilitation or regenerative processes after spinal-cord injuries or axonal damage. Furthermore, the therapies of cerebral tumors by inhibition of VEGF, or the support of neuroprotective mechanisms after ischemic insults by up-regulation of VEGF, are therapeutical options that might be of interest to future investigations.

    Related Articles | Metrics
    Intracellular sorting pathways of the amyloid precursor protein provide novel neuroprotective strategies
    Guido Hermey
    2015, 10 (11):  1727-1728.  doi: 10.4103/1673-5374.170288
    Abstract ( 268 )   PDF (233KB) ( 604 )   Save

    Alzheimer’s disease (AD) is the most common cause of senile dementia. It is characterized by the formation of plaques mainly composed of the amyloid-beta peptide (Aβ). Diverse lines of evidence support the notion that accumulation of Aβ is a primary cause of AD pathogenesis. The current analyses suggest a model in which SorCS1 is not regulating Golgi-endosomal trafficking of APP, but is regulating its sorting and anterograde transport. Small alterations in APP trafficking may have a modest impact on Aβ generation, but probably result as a long-term effect over a lifetime in dramatic Aβ? accumulation. Therefore, understanding the intracellular sorting pathways of APP and its determinants in more detail will underlie the development of novel neuroprotective strategies.

    Related Articles | Metrics
    Brain protein oxidation: what does it reflect?
    Parvana Hajieva, Bernd Moosmann
    2015, 10 (11):  1729-1730.  doi: 10.4103/1673-5374.170294
    Abstract ( 315 )   PDF (303KB) ( 557 )   Save

    Granted that the “oxidation-through-lifetime” hypothesis was correct, what consequences would emerge for future neuroprotective strategies? Most basically, humans and mice are different, even with respect to such fundamental aspects of redox homeostasis asprotein carbonyl formation. In humans, cytosolic protein oxidation appears to be much less of a problem than damage to membrane proteins, which might clearly account for the failure in humans of the exclusively aqueous double-sulfocompound NXY-059 that had been quite efficacious in rodents. Gyrencephalic animal models might provide some solution to avoid the rodent-human gap, as also mentioned in the STAIR recommendations for stroke, but it is clear that those are very much demanding. What could one still achieve in mice? Clearly, the study of protein turnover should provide significant insight. Moreover, the identification of proteins with very high baseline oxidation levels, or the search for proteins that are selectively degraded after an insult or in a disease might be more rewarding than the everlasting search for further proteins whose steady-state levels of oxidation are somewhat higher in a disease: the latter proteins might just reflect a selection of proteins whose oxidation is unusually well tolerated by the cell, such that it postpones their degradation to a later point. In the end, the study of protein oxidation in the dynamic context of turnover and site-specific degradation in the brain seems crucial, if only so for the realization of better treatment options for the primary proteolytic failure diseases.

    Related Articles | Metrics
    Brain protein oxidation: what does it reflect?
    Parvana Hajieva, Bernd Moosmann
    2015, 10 (11):  1731-1732.  doi: 10.4103/1673-5374.170294
    Abstract ( 154 )   PDF (144KB) ( 605 )   Save

    Granted that the “oxidation-through-lifetime” hypothesis was correct, what consequences would emerge for future neuroprotective strategies? Most basically, humans and mice are different, even with respect to such fundamental aspects of redox homeostasis asprotein carbonyl formation. In humans, cytosolic protein oxidation appears to be much less of a problem than damage to membrane proteins, which might clearly account for the failure in humans of the exclusively aqueous double-sulfocompound NXY-059 that had been quite efficacious in rodents. Gyrencephalic animal models might provide some solution to avoid the rodent-human gap, as also mentioned in the STAIR recommendations for stroke, but it is clear that those are very much demanding. What could one still achieve in mice? Clearly, the study of protein turnover should provide significant insight. Moreover, the identification of proteins with very high baseline oxidation levels, or the search for proteins that are selectively degraded after an insult or in a disease might be more rewarding than the everlasting search for further proteins whose steady-state levels of oxidation are somewhat higher in a disease: the latter proteins might just reflect a selection of proteins whose oxidation is unusually well tolerated by the cell, such that it postpones their degradation to a later point. In the end, the study of protein oxidation in the dynamic context of turnover and site-specific degradation in the brain seems crucial, if only so for the realization of better treatment options for the primary proteolytic failure diseases.

    Related Articles | Metrics
    Immunization with Cop-1 promotes neuroprotection and neurogenesis after ischemic stroke
    Yolanda Cruz, Paola Suárez-Meade, Antonio Ibarra
    2015, 10 (11):  1733-1734.  doi: 10.4103/1673-5374.165288
    Abstract ( 162 )   PDF (558KB) ( 387 )   Save

    A stroke occurs as a result of a disturbance or interruption of cerebral blood flow, significantly reducing the supply of oxygen and glucose to the neural tissue. Consequently, several cell death mechanisms (secondary lesion mechanisms) such as necrosis, excitotoxicity, free radical production and inflammation are trigerred. Over the last couple of decades, a variety of drugs with thrombolytic, neuroprotective, and restorative properties have been studied. However, the results of these studies appear to be limited. Thereby, there is not an entirely effective treatment for the reduction of neural damage. As of today, the first-line treatment for stroke is tissue plasminogen activator (tPA). When administered, its thrombolytic properties restore blood flow. Unfortunately; the therapeutic time window for tPA is very short, and its beneficial effects only appear if it is applied in less than 4.5 hours after an ischemic event. Innovative theurapeutic options are currently being developed in order to restore affected neuronal circuits following a cerebral ischemic event. Some of these innovative therapeutic approaches are based on stem cell transplantation and/or induction of neurogenesis. Cop-1 is an immunomodulatory drug already approved by the Food and Drug Administration (FDA) for the treatment of MS, implying that the safety of the drug has been validated. As a minimally invasive approach for treating neurological diseases involving an inflammatory response, Cop-1 has the ability to modulate inflammation and increase local neurotrophic factor production. Preliminary data has led us to believe that active immunization with Cop-1 enhances functional recovery by inducing neuroprotection and neurorestoration. These beneficial effects are achieved by avoiding autoimmune disease, local toxicity and by increasing the levels of neurotrophic factors. As an FDA-approved treatment, Cop-1 could easily be developed for treatment of clinical cerebrovascular diseases or cognitive disorders, with the objective of decreasing mortality and improving the quality of life of the patient. Therapy with Cop-1 represents a promising approach that should be explored in order to optimize the therapeutic strategy for neurodegenerative diseases in the clinical field.

    Related Articles | Metrics
    Who is who after spinal cord injury and repair? Can the brain stem descending motor pathways take control of skilled hand motor function?
    Guillermo García-Alías, V. Reggie Edgerton
    2015, 10 (11):  1735-1736.  doi: 10.4103/1673-5374.165318
    Abstract ( 229 )   PDF (244KB) ( 1016 )   Save

    Anatomical, electrophysiological and genetic studies have carefully dissected the pathways connecting the brain and the spinal cord. Lawrence and Kuypers described the organization of the descending motor pathways in the non human primate spinal cord. In spite of the differences between species regarding the precise anatomical location of each spinal pathway and the selective connectivity onto spinal interneurons and motoneurons, the pattern of organization described is conserved among the mammalian spinal cord. Based on their description, the major descending motor pathways are grouped depending on their anatomical origin and their terminal distribution pattern in the spinal grey matter. The motor cortex projects corticospinal axons to the spinal cord, which mostly run in the contralateral cord and innervate the mid and dorsal grey matter neurons. On the other hand, the spinal pathways originated in the brain stem are subdivided in the lateral and ventromedial systems. Whereas, the ventromedial system fibers are originated in the reticular formation and the vestibular complex, and terminate in the ventral and medial parts of the ventral horn grey matter, the lateral system fibers have their origin in red nucleus and preferentially terminate in the dorsal and lateral parts of the dorsal and medial grey matter. Together with the corticospinal fibres, the lateral brain-stem system contact interneurons related to motoneurons of distal muscles, whereas, ventromedial system pathways contact interneurons related to motoneurons of proximal muscles. Functionally, the corticospinal and lateral brain stem pathway are involved in the control of distal arm and hand muscles involved in skilled limb movements, the ventral brain stem pathways are mostly involved in the control the most proximal musculature of the trunk and limbs involved in posture and locomotion. Behavioral and electrophysiological studies, mostly performed in cats and non human primates corroborated these anatomical findings. Furthermore, rodents with injuries indiscrete areas of the spinal cord selectively impair specific motor functions, evidencing the functional specificity of each spinal pathways and the spinal networks innervated.

    Related Articles | Metrics
    Propriospinal interneurons in the spotlight for anatomical and functional recovery after spinal cord injury
    Martin Pohland, Jana Glumm
    2015, 10 (11):  1737-1738.  doi: 10.4103/1673-5374.170295
    Abstract ( 255 )   PDF (391KB) ( 628 )   Save

    Spinal cord injury (SCI) with consecutive paralysis below the lesion level is a severe disorder affecting the patient for the rest of his or her life. So far, there is no known fundamental intervention strategy for efficiently helping those patients regain their motor abilities, despite intense research in this area. Thus, effective treatment for those patients is still an open question. A spinal cord injury is accompanied by a primary, severe and irreversible neuronal cell death in the trauma region, followed by a secondary extensive cell necrosis in the lesion surrounding areas. Nevertheless, recent studies indicate that regeneration after spinal cord injury could be possible if three substantial steps are fulfilled: (1) reduction of the inhibitory environment at the SCI lesion site, (2) identification of a neural substrate to establish new spinal circuits, and (3) support of these circuits to form permanent, functional motor, sensory, or autonomic connections.

    Related Articles | Metrics
    Sensory regeneration in dorsal root avulsion
    Jan Hoeber
    2015, 10 (11):  1739-1740.  doi: 10.4103/1673-5374.170296
    Abstract ( 220 )   PDF (443KB) ( 816 )   Save

    Brachial as well as lumbosacral plexus avulsion injuries are usually caused by high kinetic traumas, such as car-pedestrian, car and motorcycle accidents or falls from great heights. Traction forces affecting the head and shoulders or extremities pull the spinal nerve sleeves away from the spinal cord thus tearing and rupturing the postganglionic spinal root until it is avulsed from the spinal cord. In so called central avulsion injuries, the spinal root is avulsed at the interface between the central and peripheral nervous system (CNS and PNS).  This results not only in the disconnection of the root from the cord but also in a longitudinal spinal cord injury. The complexity of the injury leads to degeneration of the spinal root and a marked inflammatory response of the spinal cord followed by the formation of a glial scar. The study provides the first evidence that sensory regeneration across the CNS-PNS interface through growth permissive gates formed by engrafted hNP spheres can be achieved also in dorsal root avulsion. The mechanism behind the formation of growth permissive gates remains elusive and topographically specific regeneration will most likely require combinatorial approaches that are able to guide sensory axons after entering the spinal cord.

    Related Articles | Metrics
    Compliant semiconductor scaffolds: building blocks for advanced neural interfaces
    Francesca Cavallo
    2015, 10 (11):  1741-1742.  doi: 10.4103/1673-5374.165297
    Abstract ( 208 )   PDF (595KB) ( 546 )   Save

    Neuroscience, neuroprosthetics and neural regeneration would benefit from more adequate in-terfacing devices. To understand how neurons communicate, process information and control behavior, researchers need to monitor nerve cell activity with high specifity and high spatio-temporal resolution. Neural prostheses require minimally invasive implantable devices to re-place lost function, and bypass dysfunctional pathways in the nervous system. Devices built to repair damaged nerves have to support and promote regeneration of host neurons through an injured area. Finally as neuromodulation is being elevated from last resort to first choice treat-ment for an increasing number of conditions, implantable devices able to perform targeted regulation of neural activity are needed. Recent advances in device miniaturization, materials engineering and nanotechnology are enabling development of an increasing number of devices that effectively interface with neural circuits. Wireless spinal cord and deep brain stimulators, retinal and cochlear implants, high density electrodes arrays for neural recording have already proven to significantly impact fundamental research in neuroscience as well as individuals’ quality of life.

    Related Articles | Metrics
    Novel approaches for the development of peripheral nerve regenerative therapies
    Felix Beyer, Patrick Küry
    2015, 10 (11):  1743-1745.  doi: 10.4103/1673-5374.170298
    Abstract ( 283 )   PDF (427KB) ( 758 )   Save

    The search for active ingredients in polyvalent immunoglobulin preparations (Fc receptor or Schwann cell antigen–directed) as well as studies of S1P receptor activation by means of more specific ligands might further pave the way for novel repair therapies for patients with different peripheral nerve conditions. The studies presented here also demonstrate that Schwann cells exert a high degree of immunocompetence and that multiple signaling interfaces between immune and Schwann cells exist, and these could be explored for pharmacological modulation.

    Related Articles | Metrics
    pFTAA: a high affinity oligothiophene probe that detects filamentous tau in vivo and in cultured neurons
    Jack Brelstaff, Maria Grazia Spillantini, Aviva M. Tolkovsky
    2015, 10 (11):  1746-1747.  doi: 10.4103/1673-5374.165298
    Abstract ( 184 )   PDF (343KB) ( 796 )   Save

    Tauopathies describe a group of neurodegenerative diseases in which the protein tau, encoded by the gene MAPT, is aberrantly misfolded, leading to tau aggregation, neural dysfunction, and cell death. In Alzheimer’s disease (AD), tau forms the characteristic intracellular neurofibrillary tangles (NFTs), which are thought to be the major cause of neurodegeneration. In other tauopathies, including frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17T), corticobasal degeneration and progressive supranuclear palsy, there are specific forms of tau aggregates and filaments without any amyloid pathology, demonstrating tau’s potent disease-causing potential. Tau is a microtubule (MT) binding protein, which becomes abnormally hyperphosphorylated on several residues prior/during the process of aggregation, thereby causing loss of its MT binding activity. The importance of tau as a single cause of disease is reinforced by the identification of numerous (>55) mutations in autosomal-dominant forms of familial tauopathies, many of which occur in the MT binding domain. Indeed, more and more diseases are being uncovered in which aberrant phosphorylation and folding of tau is implicated, such as Huntington’s disease (HD), while MAPT is a genetic risk factor for Parkinson’s disease (PD), so it is of major interest to understand how it leads to cell dysfunction and death.

    References | Related Articles | Metrics
    A role for mitogen-activated protein kinase phosphatase 1 (MKP1) in neural cell development and survival
    André Toulouse, Yvonne M. Nolan
    2015, 10 (11):  1748-1749.  doi: 10.4103/1673-5374.169606
    Abstract ( 178 )   PDF (284KB) ( 543 )   Save

    The mitogen-activated protein kinase (MAPK) pathways are a group of conserved intracellular signalling pathways present in most cells including neurons and glia. These pathways respond to a variety of stimuli including growth factors, cytokines and oxidative stress to generate appropriate cellular responses such as modulation of gene expression, cell proliferation, differentiation and survival as well as the stress response. The details of the cascades have been discussed elsewhere but usually follow a three-tier structure; a MAP3K activates a MAPK kinase (MAPKK), which in turn activates a MAPK, that can in turn regulate the activity of its cellular target by phosphorylation of specific amino acid residues. Three groups of MAPK have been identified; the extracellular signal-regulated kinases of which extracellular signal-regulated kinase (ERK)1/2 and ERK5 form two distinct classes, c-JUN N-terminal kinases (JNK1, JNK2 and JNK3), and the p38 kinases (p38 α, β, γ and δ). The ERK1/2 and ERK5 pathways respond to both mitotic and stress signals provided by growth factors, hormones and inflammatory cytokines. The other MAPK, p38 and JNK, are activated in response to growth factors, cytokines, viral proteins, lipopolysaccharides as well as cellular stress conditions. Collectively, the MAPK pathways play important roles in regulating cellular ageing, cell division, cell survival/apoptosis, neuronal activity, insulin signalling, inflammation and the immune response.

    Related Articles | Metrics
    Antiglycative activity of sulforaphane: a new avenue to counteract neurodegeneration?
    Cristina Angeloni, Marco Malaguti, Silvana Hrelia
    2015, 10 (11):  1750-1751.  doi: 10.4103/1673-5374.169613
    Abstract ( 250 )   PDF (275KB) ( 578 )   Save

    Neurodegeneration is a key aspect of a large number of diseases that come under the umbrella of “neurodegenerative diseases” with the most notable being Parkinson’s, Alzheimer’s, and Huntington’s disease. They are all incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells and are the leading cause of disability in the elderly. The incidence of these diseases is on the rise and yet there is a paucity of effective therapies to treat them. Research is now focused on understanding the mechanisms of disease in order to develop new therapies and strategies that may benefit patients suffering from any of the conditions. SF exerts pleiotropic actions on different cellular targets protecting neurons by cell death induced by MG exposure. SF action, in fact, could not be ascribed to a simple anti-glycative process, but, considering the “tandem” of free radical and MG and the fall in intracellular GSH concentration, it can modulate different cellular functions leading to a pro-survival frame of particular importance in the prevention/counteraction of multifactorial neurodegenerative diseases like AD.

    Related Articles | Metrics
    The neuroprotective and regenerative potential of parkin and GDNF/Ret signaling in the midbrain dopaminergic system
    Edgar R. Kramer
    2015, 10 (11):  1752-1753.  doi: 10.4103/1673-5374.165295
    Abstract ( 236 )   PDF (271KB) ( 566 )   Save
    Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The etiology of PD is still not completely understood, but degeneration of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc), loss of DA innervation of the striatum, and protein aggregates in form of Lewy bodies and neurites are established hallmarks. Besides α-synuclein accumulation in Lewy bodies and neurites, also genetic mutations in the genes encoding for example parkin, PINK, DJ-1 and LRRK2 proteins have been associated with the inherited form of PD and an association study linked also the receptor tyrosine kinas Ret with PD. Currently there are only symptomatic treatments available for PD and no cure. Therefore many efforts are made to find neurotrophic and other factors to stimulate SNpc DA neuron protection and regeneration. Glial cell line-derived neurotrophic factor (GDNF) is the founding member of the GDNF family of ligands (GFLs) including neurturin, artemin and persephin which belong to the transforming growth factor-β (TGF-β) superfamily. GDNF bindings with high affinity to GDNF family receptor α1 (GFRα1) that can subsequent activate the receptor tyrosine kinase Ret or alternative GDNF receptors such as the neuronal cell adhesion molecule NCAM, integrins αV and βI, syndecan-3 or N-cadherin. The canonical GDNF receptor Ret signals through many pathways such as the PI3K/Akt, Ras/MAPK, NF-κB, JNK, and PLC?/PKC pathways, while NCAM  can activate Fyn and FAK. GDNF is thought to be the most potent neurotrophic factor for the two midbrain dopaminergic (DA) neuron populations, the SNpc DA neurons dying in PD patients and the ventral tegmental area (VTA) DA neurons altered during drug addiction. Surprisingly, although GDNF stimulates neuronal differentiation, neurite outgrowth, synapse formation, and dopamine release in cell culture, GDNF was shown to be dispensable for DA neuron development and maintenance. In contrast, we could show in two different DA system specific Ret knockout mice, that Ret is dispensable during development but important for maintaining SNpc DA neurons in aging mice.
     
    Related Articles | Metrics
    Cognitive training in neurodegenerative diseases: a way to boost neuroprotective molecules?
    Francesco Angelucci*, Carlo Caltagirone, Alberto Costa
    2015, 10 (11):  1754-1755.  doi: 10.4103/1673-5374.169608
    Abstract ( 163 )   PDF (138KB) ( 524 )   Save
    Neurodegenerative diseases comprehend a series of diseases characterized by progressive and apparently irreversible loss of neurons, or loss of neuronal functionality. Although each of these diseases has certain characteristics that affect different areas of the brain with different outcomes, the common denominator is that the brain neurons undergo degeneration and subsequent death. The study of the causes of these diseases is still ongoing, and unfortunately it is not easy to find the correct path to follow. As an example, it is worth to mention the case of Alzheimer’s disease (AD) where for decades the focus was on the “amyloid cascade hypothesis” without reaching any definitive conclusions. Naturally this hypothesis remains valid today but sometimes it is necessary to undertake other directions. How, for example, to explain the fact that post-mortem studies have clearly demonstrated the presence of amyloid plaques and neurofibrillary tangles in subjects without AD symptoms? It looks like something is missing to the general opinion on the mechanisms of these diseases. Besides these general considerations and going into further detail, among many therapeutic approaches proposed and/or adopted, a common denominator is the attempt to restore, or at least limit, the damage of neuronal function. Indeed, this is currently the most logical approach to follow, because as we said before, the causes of these diseases are still unknown. In this regard, we have recently proposed a cognitive rehabilitation protocol in patients with Parkinson's disease (PD), in which we used as a possible biomarker or readout of the effects of cognitive training the serum levels of a member of a class of proteins acting on neuronal function: the neurotrophin brain-derived neurotrophic factor (BDNF).
     
    Related Articles | Metrics
    Polyphenols for the prevention and treatment of dementia diseases
    Helmut M. Hügel, Neale Jackson
    2015, 10 (11):  1756-1758.  doi: 10.4103/1673-5374.169609
    Abstract ( 220 )   PDF (552KB) ( 585 )   Save

    Diet has a dynamic molecular impact on human health. The nature and quantity of dietary intake profoundly influences cellular functions, epigenetic alterations and mechanisms that control gene expression. The ready availability and low cost of food and the freedom of being able to eat anything does not mean that we should exploit eating practices to eat everything. Carbohydrates, lipids and proteins are the primary dietary fuels that yield metabolic energy providing body function and performance, whereas dietary phytochemicals and herbal medicines rich in polyphenols are associated with a decreased risk of several human chronic diseases, sustain the cellular molecular machinery, preventing the development of disorders, gain of toxic function and disease conditions. Natural products utilized in folk medicine have demonstrated safety profiles since they have already been utilized for decades for the treatment of disease in humans and animals, we use them as templates for the generation of analogues for the development of therapeutic compounds, and probing molecular mechanisms underlying cellular dysfunction. The major liabilities of herbal medicinal products are poor biocompatibility, pharmacokinetic profiles and BBB permeability. Alkaloids, terpenes, polyphenolic compounds represent the most prevalent classes of herbal constituents with anti-dementia benefit. It is unclear to what extent many of these bioactive phytochemicals, utilized in single or herbal formulae doses can reach the brain in sufficient concentrations and in a biologically active form to exert their neuroprotective effects. For AD therapy, herbal products offer a wider range of brain-targets, nutritional benefits, safer dosage, long-term applications and efficacious treatment of AD pathology. In conclusion, despite extensive knowledge about how diet and nutrition has advanced beyond understanding cellular energy status, diet related chronic diseases of modern society are now the single largest cause of death. Epidemiological investigations indicate that nutrition and dietary patterns are modifiable risk factors that can help limit and prevent chronic diseases, enabling the achievement of the overall objective in slowing human aging diseases such as AD and thereby improving the quality of health span of everyone.

    Related Articles | Metrics
    Perspectives on neuroreparative therapies for treating multiple sclerosis
    Junhua Xiao*
    2015, 10 (11):  1759-1760.  doi: 10.4103/1673-5374.169610
    Abstract ( 240 )   PDF (154KB) ( 548 )   Save

    Multiple sclerosis (MS) is the most common neurological disease of young Caucasian adults. This disease is characterized by inflammatory demyelination of the central nervous system (CNS) and involves activation of key inflammatory cells of both the adaptive and innate immune systems, which target and destroy both myelin and oligodendrocytes (the myelin-forming glial cells in the CNS). Key pathological features of the disease include autoimmune inflammation, demyelination (myelin loss) and axonal degeneration. The key cell type damaged in MS is oligodendrocytes, which produce the insulating myelin sheath surrounding many axons in the CNS. Myelin and oligodendrocytes have critical roles. Myelin is responsible for promoting rapid, saltatory conduction of action potentials throughout much of the CNS. When myelin is lost in diseases such as MS, saltatory conduction is disrupted and conduction block can ensue. Myelin also provides a physical barrier for axons and thus serves to abrogate axonally directed, immune attack. Oligodendrocytes can also provide key nutritive support to axons in the healthy, quiescent state, which is compromised when oligodendrocytes are targeted. There is an emerging consensus that the progressive disability that ultimately ensues for many patients with MS correlates with the degree of accumulative axonal degeneration. It is also apparent that the extent of demyelination, and the degree of oligodendrocyte targeting, are likely to be relevant factors that dictate outcomes. Whilst it is well identified that spontaneous remyelination occurs after a demyelinative insult, the degree of remyelination within MS lesions is variable; generally MS lesions remyelinate relatively efficiently early on in disease; however, at later stages many lesions remain chronically demyelinated. These chronically demyelinated lesions typically contain oligodendrocyte progenitor cells (OPCs) and premyelinating oligodendrocytes that have “stalled” in their differentiation. These findings suggest remyelination is not limited by an absence of oligodendrocyte progenitors or their failure to generate oligodendrocytes, but a failure to differentiate into mature oligodendrocytes and to initiate new myelin formation.

    Related Articles | Metrics
    Chemotactic signaling and beyond: link between interleukin-16 and axonal degeneration in multiple sclerosis
    Dusanka S. Skundric
    2015, 10 (11):  1761-1763.  doi: 10.4103/1673-5374.165294
    Abstract ( 199 )   PDF (466KB) ( 565 )   Save

    Multiple sclerosis (MS) is progressive inflammatory, and chronic demyelinating, neurodegenerative disease of central nervous system (CNS). Autoimmune responses to myelin and other CNS antigens mediated by CD4+ T cells are critical for initiation and progression of disease.Migration of autoimmune T cells from the peripheral lymph organs into CNS parenchyma leads to inflammation, demyelination and damage of axonal cytoskeleton, which manifest indecreased impulse conduction velocity of motor and sensory nerves. Myelin and axonal pathology causes motor, sensory and autonomic nerve dysfunction, including paresis and paralysis of extremities, painful sensations, and bladder sphincter dysfunction, manifested as incontinence. Gray matter pathology in cortical and subcortical regions, including cerebellum and hippocampus underlies cognitive and behavioral dysfunctioncomprisingof among other, memory deficits, depression, and ataxic gait. Multifaceted cellular and molecular mechanisms involved in autoimmune – mediated inflammation, demyelination, and subsequent degeneration of axonal cytoskeleton as well asneuronal cell dysfunction and demise, have been researched in experimental autoimmune encephalomyelitis (EAE). With the development of new EAE models, significance of EAE in MS studies continues to be reexamined and the importance of similarity between two diseases to be highlighted. This autoimmune experimental model is regularly used in development and preclinical testing of MS therapy aimed at treating or ameliorating autoimmune responses observed in MS, with an ultimate goal to cure or diminish tissue damage and support axonal regeneration and repair.

    Related Articles | Metrics
    Fetal alcohol spectrum disorder: molecular insights into neural damage reduction
    Diana Le Duc
    2015, 10 (11):  1764-1766.  doi: 10.4103/1673-5374.165290
    Abstract ( 203 )   PDF (293KB) ( 597 )   Save

    Fetal Alcohol Spectrum Disorders (FASD) is a group of entirely preventable, lifelong conditions, which occur upon maternal alcohol use during pregnancy. This can result in severe consequences for the newborn and ultimately the family. It is usually characterized by delays in development and motor function, craniofacial abnormalities, and difficulties with learning, memory, speech, and academic achievement. According to the German guidelines for fetal alcohol syndrome (FAS) diagnosis, the prevalence of FASD ranges between 0.02–0.8% of all annual births and often the disorder is not recognized. The U.S. National Institutes of Health regard FAS as the most common nonhereditary cause of mental retardation. Thus, preventing programs, like the one undertaken by the Australian Government, which appointed a National FASD Technical Network, may seem a very reasonable strategy. However, preventing programs for FASD focus mainly either on primary prevention, by increasing pregnant women’s awareness of ethanol consumption risks, or on tertiary prevention which supposes early recognition of the condition and social support in the form of an improved developmental framework of the affected individual. Secondary prevention of the disorder, which includes early detection by screening and treatment of the pre clinical pathological conditionis considered to be most challenging. This form of prevention could prove useful in the treatment and control of FAS progression, but therapy approaches are hindered by our limited knowledge of molecular mechanisms responsible for neuronal damage.

    Related Articles | Metrics
    Two sides of the same coin: tyrosine kinase inhibitionin cancer and neurodegeneration
    Michaeline Hebron, Charbel E-H Moussa
    2015, 10 (11):  1767-1769.  doi: 10.4103/1673-5374.165320
    Abstract ( 252 )   PDF (452KB) ( 605 )   Save
    Cancer and neurodegeneration include a group of diseases that are mechanistically distinct but may share common therapeutic targets. Both cancer and neurodegeneration may propagate by contiguity, leading to disease spread from one body part to another. Autophagy is a common quality control mechanism shared by mitotic and post-mitotic cells and it can be exploited to accelerate clearance of unwanted oncogenes and reduce accumulation of toxic proteins in cancer and neurodegeneration, respectively. Tyrosine kinase inhibition is a therapeutically relevant strategy that can induce autophagy, leading to normal cell survival in certain type of cells. This perspective provides insights into how tyrosine kinase inhibition can be clinically used to arrest mitotic cell division and tumor growth, while promoting survival of post-mitotic neurons. As modulators of myeloid cells, TKIs may also positively regulate neuronal death and produce neuro-restorative effects, independent of brain concentration, via production of necessary growth factors and proliferation of myeloid-derived glial cells. Autophagictoxic protein clearance and production of growth factors may restore fluctuations of neurotransmitters, leading to alterations of motor and cognitive functions. Tyrosine kinase inhibition provides a double-edge sword via manipulation of autophagy to inhibit cell division and tumor growth in cancer on one hand, and promote toxic protein degradation and neuronal survival in neurodegeneration on the other hand.
     
    Related Articles | Metrics
    Factors influencing the spinal motoneurons in development
    Stefan Wiese
    2015, 10 (11):  1773-1776.  doi: 10.4103/1673-5374.169639
    Abstract ( 248 )   PDF (927KB) ( 765 )   Save
     The development of the spinal cord needs a concerted interaction of transcription factors ac¬tivating diverse genes and signals from outside acting on the specification of the different cells. Signals have to act on the segments of the embryo as well as on the cranial-caudal axis and the dorso-ventral axis. Additionally the axons of the motoneurons have to cross the central nervous system barrier to connect to the periphery. Intensive anatomical studies have been followed by molecular characterization of the different subsets of transcription factors that are expressed by cells of the developing spinal cord. Here, intensive studies for the most important appearing cells, the motoneurons, have resulted in a good knowledge on the expression patterns of these pro¬teins. Nonetheless motoneurons are by far not the only important cells and the concert activity of all cells besides them is necessary for the correct function and integrity of motoneurons within the spinal cord. This article will briefly summarize the different aspects on spinal cord develop¬ment and focuses on the differentiation as well as the functionalization of motoneurons.
     
    Related Articles | Metrics
    Repair, protection and regeneration of peripheral nerve injury
    Shan-lin Chen, Zeng-gan Chen, Hong-lian Dai, Jian-xun Ding,Jia-song Guo, Na Han, Bao-guo Jiang, Hua-jun Jiang, Juan Li, Shi-pu Li, Wen-jun Li, Jing Liu, Jun-xiong Ma, Jiang Peng#, *, Guang-wei Sun, Yun-dong Shen, Pei-fu Tang, Yang Liu# Gu-heng Wang, Xiang-hai Wang, Liang-bi Xiang, Ren-guo Xie, Jian-guang Xu, Bin Yu, Li-cheng Zhang, Pei-xun Zhang, Song-lin Zhou
    2015, 10 (11):  1777-1798.  doi: 10.4103/1673-5374.170301
    Abstract ( 209 )   PDF (2699KB) ( 817 )   Save
    Related Articles | Metrics
    MicroRNAs: a novel promising therapeutic target for cerebral ischemia/reperfusion injury?
    Xiao-li Min, Ting-yong Wang, Yi Cao, Jia Liu, Jin-tao Li, Ting-hua Wang
    2015, 10 (11):  1799-1808.  doi: 10.4103/1673-5374.170302
    Abstract ( 244 )   PDF (3382KB) ( 947 )   Save

    To determine the molecular mechanism of cerebral ischemia/reperfusion injury, we examined the microRNA (miRNA) expression profile in rat cortex after focal cerebral ischemia/reperfusion
    injury using miRNA microarrays and bioinformatic tools to systematically analyze Gene Ontology (GO) function classifications, as well as the signaling pathways of genes targeted by these differentially expressed miRNAs. Our results show significantly changed miRNA expression profiles in the reperfusion period after focal cerebral ischemia, with a total of 15 miRNAs up-regulated
    and 44 miRNAs down-regulated. Target genes of these differentially expressed miRNAs were mainly involved in metabolic and cellular processes, which were identified as hub nodes of a miRNA-GO-network. The most correlated pathways included D-glutamine and D-glutamate metabolism, the renin-angiotensin system, peroxisomes, the PPAR signaling pathway, SNARE interactions in vesicular transport, and the calcium signaling pathway. Our study suggests that miRNAs play an important role in the pathological process of cerebral ischemia/reperfusion injury. Understanding miRNA expression and function may shed light on the molecular mechanism
    of cerebral ischemia/reperfusion injury.

    Related Articles | Metrics
    Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset
    Xin-hong Jiang, Ke-xu Lin, Yi-xian Zhang, Rong-hua Chen, Nan Liu
    2015, 10 (11):  1809-1813.  doi: 10.4103/1673-5374.170308
    Abstract ( 139 )   PDF (493KB) ( 897 )   Save

    Evidence suggests that interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites -1082 (A/G) and -819 (C/T) in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction (cerebral infarction group) and 115 healthy subjects (control group). We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups (χ2 = 6.643, P = 0.010). The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group (92.3%) than in the control group (86.1%) (P = 0.015). Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype (OR = 2.031, 95%CI: 1.134–3.637). In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction (OR = 2.073, 95%CI: 1.278–3.364). No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups (P > 0.05). These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.

    Related Articles | Metrics
    Lentivirus-mediated Persephin over-expression in Parkinson’s disease rats
    Xiao-feng Yin, Hua-min Xu, Yun-xia Jiang, Yun-lai Zhi, Yu-xiu Liu, Heng-wei Xiang, Kai Liu, Xiao-dong Ding, Peng Sun
    2015, 10 (11):  1814-1818.  doi: 10.4103/1673-5374.170309
    Abstract ( 193 )   PDF (762KB) ( 804 )   Save

    Persephin, together with glial cell line-derived neurotrophic factor and neurturin, has a neurotrophic
    effect and promotes the survival of motor neurons cultured in vitro. In this study, dopaminergic neurons in the substantia nigra of rats were transfected with the Persephin gene. One week later 6-hydroxydopamine was injected into the anterior medial bundle to establish a Parkinson’s
    disease model in the rats. Results found that the number of dopaminergic neurons in the substantia nigra increased, tyrosine hydroxylase expression was upregulated and concentrations of dopamine and its metabolites in corpus striatum were increased after pretreatment with Persephin gene. In addition, the rotating effect of the induced Parkinson’s disease rats was much less in the group pretreated with the Persephin gene. Persephin has a neuroprotective effect on the 6-hydroxydopamine-induced Parkinson’s disease through protecting dopaminergic neurons.

    Related Articles | Metrics
    Leuprolide acetate induces structural and functional recovery of injured spinal cord in rats.
    Carmen Díaz Galindo, Beatriz Gómez-González, Eva Salinas, Denisse Calderón-Vallejo, Irma Hernández-Jasso, Eduardo Bautista
    2015, 10 (11):  1819-1824.  doi: 10.4103/1673-5374.170311
    Abstract ( 196 )   PDF (1797KB) ( 861 )   Save

    Gonadotropin-releasing hormone (GnRH) and its synthetic analog leuprolide acetate, a GnRH agonist, have neurotrophic properties. This study was designed to determine whether administration of leuprolide acetate can improve locomotor behavior, gait, micturition reflex, spinal cord morphology and the amount of microglia in the lesion epicenter after spinal cord injury in rats. Rats with spinal cord compression injury were administered leuprolide acetate or saline solution for 5 weeks. At the 5th week, leuprolide acetate-treated rats showed locomotor activity recovery by 38%, had improvement in kinematic gait and exhibited voiding reflex recovery by 60%, as compared with the 1st week. By contrast, saline solution-treated rats showed locomotor activity recovery only by 7%, but voiding reflex did not recover. More importantly, leuprolide acetate treatment reduced microglial immunological reaction and induced a trend towards greater area of white and gray matter in the spinal cord. Therefore, leuprolide acetate has great potential to repair spinal cord injury.

    Related Articles | Metrics
    Does the intrathecal propofol have a neuroprotective effect on spinal cord ischemia?
    Murat Sahin, Huriye Gullu, Kemal Peker, Ilyas Sayar, Orhan Binici, Huseyin Yildiz
    2015, 10 (11):  1825-1829.  doi: 10.4103/1673-5374.170312
    Abstract ( 144 )   PDF (892KB) ( 815 )   Save

    The neuroprotective effects of propofol have been confirmed. However, it remains unclear whether intrathecal administration of propofol exhibits neuroprotective effects on spinal cord ischemia. At 1 hour prior to spinal cord ischemia, propofol (100 and 300 μg) was intrathecally administered in rats with spinal cord ischemia. Propofol pre-treatment greatly improved rat pathological changes and neurological function deficits at 24 hours after spinal cord ischemia. These results suggest that intrathecal administration of propofol exhibits neuroprotective effects on spinal cord structural and functional damage caused by ischemia.

    Related Articles | Metrics
    Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury
    Mu Jin, Yan-wei Yang, Wei-ping Cheng, Jia-kai Lu, Si-yu Hou, Xiu-hua Dong, Shi-yao Li
    2015, 10 (11):  1830-1835.  doi: 10.4103/1673-5374.170313
    Abstract ( 148 )   PDF (1841KB) ( 582 )   Save

    The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.

    Related Articles | Metrics
    Combination of fasudil and celecoxib promotes the recovery of injured spinal
    Xiao-lin Hou, Yan Chen, Hua Yin, Wei-gang Duan
    2015, 10 (11):  1836-1840.  doi: 10.4103/1673-5374.170314
    Abstract ( 378 )   PDF (1346KB) ( 876 )   Save

    Resistance mechanisms of rho-associated kinase (ROCK) inhibitors are associated with the enhanced expression of cyclooxygenase-2 (COX-2). The therapeutic effects of ROCK on nervous system diseases might be enhanced by COX-2 inhibitors. This study investigated the synergistic effect of the combined use of the ROCK inhibitor fasudil and a COX-2 inhibitor celecoxib on spinal cord injury in a rat model established by transecting the right half of the spinal cord at T11. Rat models were orally administrated with celecoxib (20 mg/kg) and/or intramuscularly with fasudil (10 mg/kg) for 2 weeks. Results demonstrated that the combined use of celecoxib and fasudil significantly decreased COX-2 and Rho kinase II expression surrounding the lesion site in rats with spinal cord injury, improved the pathomorphology of the injured spinal cord, and promoted the recovery of motor function. Moreover, the effects of the drug combination were better than celecoxib or fasudil alone. This study demonstrated that the combined use of fasudil and celecoxib synergistically enhanced the functional recovery of injured spinal cord in rats.

    Related Articles | Metrics
    Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica
    Adriana Octaviana Dulamea, Mirela-Patricia Sirbu-Boeti, Coralia Bleotu, Denisa Dragu, Lucia Moldovan, Ioana Lupescu
    2015, 10 (11):  1841-1845.  doi: 10.4103/1673-5374.165325
    Abstract ( 350 )   PDF (2373KB) ( 880 )   Save

    Recent studies provided evidence that mesenchymal stem cells (MSCs) have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica (NMO) is an autoimmune, demyelinating
    central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers (PUs) on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient’s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms
    in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

    Related Articles | Metrics
    Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury
    Hong-fei Li, Yi-ru Wang, Hui-ping Huo, Yue-xiang Wang, Jie Tang
    2015, 10 (11):  1846-1855.  doi: 10.4103/1673-5374.170315
    Abstract ( 156 )   PDF (5321KB) ( 1108 )   Save

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

    Related Articles | Metrics
    Single injection of platelet-rich plasma as a novel treatment of carpal tunnel syndrome
    Michael Alexander Malahias, Elizabeth O. Johnson, George C. Babis, Vasileios S. Nikolaou
    2015, 10 (11):  1856-1859.  doi: 10.4103/1673-5374.165322
    Abstract ( 216 )   PDF (380KB) ( 874 )   Save

    Both in vitro and in vivo experiments have confirmed that platelet-rich plasma has therapeutic effects on many neuropathies, but its effects on carpal tunnel syndrome remain poorly understood. We aimed to investigate whether single injection of platelet-rich plasma can improve the clinical symptoms of carpal tunnel syndrome. Fourteen patients presenting with median nerve injury who had suffered from mild carpal tunnel syndrome for over 3 months were included in this study. Under ultrasound guidance, 1–2 mL of platelet-rich plasma was injected into the region around the median nerve at the proximal edge of the carpal tunnel. At 1 month after single injection of platelet-rich plasma, Visual Analogue Scale results showed that pain almost disappeared in eight patients and it was obviously alleviated in three patients. Simultaneously, the disabilities of the arm, shoulder and hand questionnaire showed that upper limb function was obviously improved. In addition, no ultrasonographic manifestation of the carpal tunnel syndrome was found in five patients during ultrasonographic measurement of the width of the median nerve. During 3-month follow-up, the pain was not greatly alleviated in three patients. These findings show very encouraging mid-term outcomes regarding use of platelet-rich plasma for the treatment of carpal tunnel syndrome.
    :

    Related Articles | Metrics
    Changes in lumbosacral spinal nerve roots on diffusion tensor imaging in spinal stenosis
    Zhong-jun Hou, Yong Huang, Zi-wen Fan, Xin-chun Li, Bing-yi Cao
    2015, 10 (11):  1860-1864.  doi: 10.4103/1673-5374.170317
    Abstract ( 144 )   PDF (980KB) ( 674 )   Save

    Lumbosacral degenerative disc disease is a common cause of lower back and leg pain. Conventional T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) scans are commonly used to image spinal cord degeneration. However, these modalities are unable to image the entire lumbosacral spinal nerve roots. Thus, in the present study, we assessed the potential of diffusion tensor imaging (DTI) for quantitative assessment of compressed lumbosacral spinal nerve roots. Subjects were 20 young healthy volunteers and 31 patients with lumbosacral stenosis. T2WI showed that the residual dural sac area was less than two-thirds that of the corresponding normal area in patients from L3 to S1 stenosis. On T1WI and T2WI, 74 lumbosacral spinal nerve roots from 31 patients showed compression changes. DTI showed thinning and distortion in 36 lumbosacral spinal nerve roots (49%) and abruption in 17 lumbosacral spinal nerve roots (23%). Moreover, fractional anisotropy values were reduced in the lumbosacral spinal nerve roots of patients with lumbosacral stenosis. These findings suggest that DTI can objectively and quantitatively evaluate the severity of lumbosacral spinal nerve root compression.

    Related Articles | Metrics
    Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia
    Xu-yang Wang, Pei-yuan Gu, Shi-wen Chen, Wen-wei Gao, Heng-li Tian, Xiang-he Lu, Wei-ming Zheng, Qi-chuan Zhuge
    2015, 10 (11):  1865-1868.  doi: 10.4103/1673-5374.170318
    Abstract ( 166 )   PDF (1474KB) ( 863 )   Save

    In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1–5 and L7–S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin- 3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

    Related Articles | Metrics
    Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords
    Norihiro Nishida, Tsukasa Kanchiku, Junji Ohgi, Kazuhiko Ichihara, Xian Chen, Toshihiko Taguchi
    2015, 10 (11):  1869-1873.  doi: 10.4103/1673-5374.170319
    Abstract ( 178 )   PDF (623KB) ( 994 )   Save

    No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s–1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone.

    Related Articles | Metrics
    Injury of corticoreticular pathway and corticospinal tract caused by ventriculoperitoneal shunting
    Sung Ho Jang, Jeong Pyo Seo
    2015, 10 (11):  1874-1875.  doi: 10.4103/1673-5374.170320
    Abstract ( 204 )   PDF (905KB) ( 723 )   Save
    Related Articles | Metrics
    Injury of corticoreticular pathway and corticospinal tract caused by ventriculoperitoneal shunting
    Jae Woon Kim, Han Do Lee, Sung Ho Jang
    2015, 10 (11):  1876-1878.  doi: 10.4103/1673-5374.170321
    Abstract ( 249 )   PDF (428KB) ( 708 )   Save

    Severe bilateral anterior cingulum injury in patients with mild traumatic brain injury

    Related Articles | Metrics
    Susceptibility weighted imaging in the evaluation of hemorrhagic diffuse axonal injury
    Jing-jing Tao, Wei-jiang Zhang, Dong Wang, Chun-juan Jiang
    2015, 10 (11):  1879-1881.  doi: 10.4103/1673-5374.170322
    Abstract ( 273 )   PDF (762KB) ( 707 )   Save
    Related Articles | Metrics
    Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke
    Qi-jin Yu, Hong Tao, Xin Wang, Ming-chang Li
    2015, 10 (11):  1882-1891.  doi: 10.4103/1673-5374.170324
    Abstract ( 263 )   PDF (346KB) ( 937 )   Save

    Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions.

    Related Articles | Metrics
    The role of the Rho/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system
    Jing Liu, Hong-yan Gao, Xiao-feng Wang
    2015, 10 (11):  1892-1896.  doi: 10.4103/1673-5374.170325
    Abstract ( 126 )   PDF (325KB) ( 696 )   Save

    The Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) pathway is a major signaling pathway in the central nervous system, transducing inhibitory signals to block regeneration. After central nervous system damage, the main cause of impaired regeneration is the presence of factors that strongly inhibit regeneration in the surrounding microenvironment. These factors signal through the Rho/ROCK signaling pathway to inhibit regeneration. Therefore,
    a thorough understanding of the Rho/ROCK signaling pathway is crucial for advancing studies on regeneration and repair of the injured central nervous system.

    Related Articles | Metrics