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    28 September 2015, Volume 10 Issue 9 Previous Issue    Next Issue
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    Neuroinflammation and comorbidities are frequently ignored factors in CNS pathology
    Raluca Elena Sandu, Ana Maria Buga, Adriana Uzoni, Eugen Bogdan Petcu, Aurel Popa-Wagner
    2015, 10 (9):  1349-1355.  doi: 10.4103/1673-5374.165208
    Abstract ( 224 )   PDF (336KB) ( 727 )   Save

    Virtually all drug interventions that have been successful pre-clinically in experimental stroke have failed to prove their efficacy in a clinical setting. This could be partly explained by the complexity and heterogeneity of human diseases as well as the associated co-morbidities which may render neuroprotective drugs less efficacious in clinical practice. One aspect of crucial importance in the physiopathology of stroke which is not completely understood is neuroinflammation. At the present time, it is becoming evident that subtle, but continuous neuroinflammation can provide the ground for disorders such as cerebral small vessel disease. Moreover, advanced aging and a number of highly prevalent risk factors such as obesity, hypertension, diabetes and atherosclerosis could act as “silent contributors” promoting a chronic proinflammatory state. This could aggravate the outcome of various pathological entities and can contribute to a number of subsequent post-stroke complications such as dementia, depression and neurodegeneration creating a pathological vicious cycle. Moreover, recent data suggests that the inflammatory process might be closely linked with multiple neurodegenerative pathways related to depression. In addition, pro-inflammatory cytokines could play a central role in the pathophysiology of both depression and dementia.

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    Cell replacement therapy for central nervous system diseases
    Danju Tso, Randall D. McKinnon
    2015, 10 (9):  1356-1358.  doi: 10.4103/1673-5374.165209
    Abstract ( 217 )   PDF (189KB) ( 698 )   Save

    The brain and spinal cord can not replace neurons or supporting glia that are lost through traumatic injury or disease. In pre-clinical studies, however, neural stem and progenitor cell transplants can promote functional recovery. Thus the central nervous system is repair competent but lacks endogenous stem cell resources. To make transplants clinically feasible, this field needs a source of histocompatible, ethically acceptable and non-tumorgenic cells. One strategy to generate patient-specific replacement cells is to reprogram autologous cells such as fibroblasts into pluripotent stem cells which can then be differentiated into the required cell grafts. However, the utility of pluripotent cell derived grafts is limited since they can retain founder cells with intrinsic neoplastic potential. A recent extension of this technology directly reprograms fibroblasts into the final graftable cells without an induced pluripotent stem cell intermediate, avoiding the pluripotent caveat. For both types of reprogramming the conversion efficiency is very low resulting in the need to amplify the cells in culture which can lead to chromosomal instability and neoplasia. Thus to make reprogramming biology clinically feasible, we must improve the efficiency. The ultimate source of replacement cells may reside in directly reprogramming accessible cells within the brain.

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    Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping
    Christopher Lawton, Sandra Acosta, Nate Watson, Chiara Gonzales-Portillo, Theo Diamandis, Naoki Tajiri, Yuji Kaneko, Paul R. Sanberg, Cesar V. Borlongan
    2015, 10 (9):  1359-1362.  doi: 10.4103/1673-5374.165218
    Abstract ( 245 )   PDF (183KB) ( 748 )   Save

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant’s susceptibility to both neonatal and age-related diseases.

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    PTEN inhibition and axon regeneration and neural repair
    Yosuke Ohtake, Umar Hayat, Shuxin Li
    2015, 10 (9):  1363-1368.  doi: 10.4103/1673-5374.165496
    Abstract ( 213 )   PDF (429KB) ( 1218 )   Save

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to control the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in conditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Importantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

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    The choline pathway as a strategy to promote central nervous system (CNS) remyelination
    Thomas Skripuletz, Ralf A. Linker, Martin Stangel
    2015, 10 (9):  1369-1370.  doi: 10.4103/1673-5374.165498
    Abstract ( 247 )   PDF (359KB) ( 803 )   Save

    The choline pathway as a strategy to promote CNS remyelination
    CDP-choline showed repair promoting functions in two animal models of multiple sclerosis with a new mechanism of action. Due to the known beneficial safety profile, CDP-choline may be a promising substance for patients with multiple sclerosis, which is worth further investigations e.g., as add-on therapy to established immunmodulators.  

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    Non-steroidal anti-inflammatory drugs (NSAIDs) and neuroprotection in the elderly: a view from the mitochondria
    María Calvo-Rodríguez, Lucía Núñez, Carlos Villalobos
    2015, 10 (9):  1371-1372.  doi: 10.4103/1673-5374.165219
    Abstract ( 236 )   PDF (441KB) ( 737 )   Save

    The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. Thus, recovery after brain artery occlusion is dramatically worsened with aging and even normal aging is also associated with neuron damage and cognitive decline. Mechanisms by which aging promotes cognitive decline and susceptibility to neuron damage in stroke and neurodegeneration are largely unknown. One of the most important mechanisms contributing to neural dysfunction and death is excitotoxicity. This process, initially proposed by Olney in 1969, is based in that the excessive stimulation of glutamate receptors leads to hyperactivation and neuronal damage. This overstimulation may be due to increased concentration of glutamate, or prolonged activation of the receptors by a mild increase in the concentration of the excitatory amino acid.
    Protecting the aging brain against damage remains a big challenge for neurologists and neuroscientists. Interestingly, a large number of basic and clinical studies have provided strong evidence indicating that the prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of Alzheimer's Disease, the most common form of dementia. NSAIDs also decrease glutamate excitotoxicity both in vitro, in rat primary neuronal cultures and hippocampal slices, and in vivo, protecting rats against rotenone-induced parkinsonism. Recent evidence suggests that NSAIDs may even protect against the cognitive decline associated to healthy aging in humans.

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    Neural correlates of the Heidelberg Music Therapy: indicators for the regeneration of auditory cortex in tinnitus patients?
    Christoph M. Krick, Heike Argstatter
    2015, 10 (9):  1373-1375.  doi: 10.4103/1673-5374.165220
    Abstract ( 315 )   PDF (363KB) ( 810 )   Save

    Tinnitus, the phenomenon of ringing or buzzing in the ears without an external sound source has evolved into one of the most common symptoms in otorhinolaryngology. It affects about 10 to 15% of the general population. There are now plausible models for neural basis of tinnitus, its pathogenesis and its consequences on mental health: Peripheral sensory deprivation due to cochlear damages may prompt increased neuronal activity in the central auditory system in order to adapt the neural sensitivity to the reduced sensory inputs. This central gain could over amplify the “neural noise” and thus trigger a homeostatic down-regulation of inhibitory synapses in the auditory cortical map leading to specific reorganization of the cortical representation of the tinnitus percept. Dysfunctional feedback connections from limbic regions to auditory brain areas, interacting at the thalamic level, may account for the psychological impairment.

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    Neurochemical plasticity of Müller cells after retinal injury: overexpression of GAT-3 may potentiate excitotoxicity
    Clarissa S. Schitine, Fernando G. de Mello, Ricardo A.M. Reis
    2015, 10 (9):  1376-1378.  doi: 10.4103/1673-5374.165224
    Abstract ( 337 )   PDF (461KB) ( 675 )   Save

    The retina is a multilayered tissue that develops following a central-to-peripheral gradient. Its structure derives from multipotent precursors, as shown through clonal analysis of retinal cells lineage. These progenitors generate diverse cell types, controlled by complex influences of intrinsic and extrinsic factors.
    Several types of neurons and one main glia cell constitute the vertebrate retina, constructed in a highly organized manner. Müller cell is the predominant glia of the retina and the last cell type to differentiate. Upon damage or under the influence of growth factors stimulation, they proliferate, de-differentiate and can become a source of new neurons for retina regeneration in different vertebrates. The recent data suggest that in vivo lesions of the retina induced by excitotoxic insults may be potentiated by decreased inhibitory tonus, due to increased GABA uptake by Müller cells overexpressing GAT-3. Further investigations are necessary to reveal the molecular mechanisms involved in glutamate-dependent GAT-3 plasma membrane level reduction. Interestingly however, their observations open the possibility of using GABA transport inhibitors to prevent RGCs degeneration eventually caused by reactive gliosis that follow retina degeneration.

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    Can progesterone be a better alternative to dexamethasone for use in routine brain surgery?
    Stephen Y. Cheng, Gilberto K. K. Leung
    2015, 10 (9):  1379-1380. 
    Abstract ( 353 )   PDF (152KB) ( 562 )   Save
    Surgical brain injury (SBI) is a form of brain trauma caused by various forms of neurosurgical interventions including brain tumor excision, evacuation of intracerebral hemorrhage and brain lobectomy (e.g., in epilepsy surgery). Cerebral edema and brain swelling typically occurs soon after SBI and commonly peaks on post-operative day 3 to 7. SBI may cause secondary damages due to disruption of the blood–brain barrier (BBB), release of inflammatory cytokines (e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, toll-like receptor (TLR-2) and TLR-4,) as well as increased expressions of Fas and Fas-L, free radical overload, dysfunctions of membrane ionic pumps and many other pathophysiological changes. Severe cerebral edema may eventually lead to elevated intracranial pressure (ICP), neurological deterioration or even death. Other long-term effects in survivors include sensori-motor and cognitive dysfunctions due to secondary, delayed degenerative changes. Given the large number of routine neurosurgical operations performed world-wide on a day-to-day basis, the prevention of SBI is just as important as the treatment of accident-related traumatic brain injury (TBI). The latter differs from SBI in that it is not amendable to pre-emptive therapy whereas SBI can theoretically be prevented, at least during routine elective surgery. The issue of how best to prevent cerebral edema and secondary damages in these situations are critical and deserve our research effort.
    Traditionally, dexamethasone (DEXA) and other glucocorticoids (GCs) have been used as adjunctive agents during neurosurgical operations to reduce brain edema, maintain BBB integrity and minimize inflammatory responses. It has also been used in TBI patients since 1960s. However, several major studies conducted between 1979 and 2004 demonstrated that the use of GCs in severe TBI had no beneficial effect and may in fact be deleterious. Given that SBI is essentially a form of brain traumaalso, there is no logical reason why GCs should be beneficial in SBI. In this respect, our group has been investigating alternative strategies for the treatment of SBI.
     
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     Adipose-brain crosstalk: do adipokines have a role in neuroprotection?
    Jonathan P. Little, Adeel Safdar
    2015, 10 (9):  1381-1382.  doi: 10.4103/1673-5374.165222
    Abstract ( 229 )   PDF (139KB) ( 685 )   Save

    Accumulating evidence from epidemiological and experimental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline. The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role. The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite brings about the intriguing possibility that adipose-brain crosstalk could be involved in obesity-related neurodegeneration. Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communicate directly with the brain. Research in this area is relatively new, but some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in maintenance of neuronal viability.

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    Shine bright: considerations on the use of fluorescent substrates in living monoaminergic neurons in vitro
    Patrick Schloss, Friederike Matthäus, Thorsten Lau
    2015, 10 (9):  1383-1385.  doi: 10.4103/1673-5374.165223
    Abstract ( 206 )   PDF (523KB) ( 682 )   Save

    The biogenic monoamines dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) are major neuromodulators in the mammalian central nervous system (CNS). DA containing neurons are found in i) the mesolimbic system in which cell bodies in the ventral tegmental area (VTA) project axons into the amygdala, cortex, hippocampus and the nucleus accumbens; and ii) the nigrostriatal system in which cell bodies located in the substantia nigra pars compacta send their axons into the dorsolateral parts of the striatum. The central noradrenergic neurons are concentrated in distinct brainstem nuclei with the locus coeruleus (LC) being the most prominent nucleus which projects a diffusely arborizing axonal network to most areas of the CNS. Serotonergic neurons are located in the raphe nuclei in the brain stem with widespread efferent axonal trajectories with a high number of collateral arborizations into many brain regions such as cortical areas, the hippocampus, the basal ganglia and the spinal cord. Malfunctions of the three monoaminergic systems are associated with different psychiatric and neurological diseases such as depression, anxiety, chronic pain, sleep disorders, schizophrenia, various aspects of drug abuse, Parkinson’s disease and Alzheimer’s disease.

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    The changes of oligodendrocytes induced by anesthesia during brain development
    Danye Jiang, Sanghee Lim, Minhye Kwak, Yun Kyoung Ryu, C. David Mintz
    2015, 10 (9):  1386-1387.  doi: 10.4103/1673-5374.165244
    Abstract ( 172 )   PDF (149KB) ( 576 )   Save

    With the advent of modern techniques, drugs, and monitoring, general anesthesia has come to be considered an unlikely cause of harm, particularly for healthy patients. While this is largely true, newly emerging clinical and laboratory studies have suggested that exposure to anesthetic agents during early childhood may have long-lasting adverse effects on cognitive function. The evidence strongly suggests that glia are a possible target of anesthetic toxicity. Astrocytes clearly undergo cytoskeletal disruption as a result of early anesthetic exposure and their capacity to support neuronal growth is transiently impaired. These results have been obtained using dissociated culture models, and must still be translated to the context of the intact brain. Anesthetics induce apoptotic cell death in a substantial population of oligodendrocytes in the developing brain, but the significance of this finding will be greatly enhanced if it is shown to be persistent. The currently available literature on the effects of anesthetics on glia in the developing brain is fairly sparse compared to studies of developmental anesthetic toxicity in neurons, and we conclude that this is a promising area for further study in the field of pediatric anesthetic neurotoxicity.

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    The roles of tubulin-folding cofactors in neuronal morphogenesis and disease
    Misako Okumura, Masayuki Miura, Takahiro Chihara
    2015, 10 (9):  1388-1389.  doi: 10.4103/1673-5374.165226
    Abstract ( 204 )   PDF (329KB) ( 681 )   Save

    Microtubules play important roles in neuronal morphogenesis, including cellular polarization, neurite growth, and branching. A microtubule is a polymer of α- and β-tubulin heterodimers that are formed by a multistep process assisted by at least five tubulin-folding cofactors (TBCA–E). Microtubule dynamics regulated by microtubule-associated proteins are important for neural development. Growing evidence suggests that regulation of the amount of free tubulins helps modulate microtubule dynamics. As have described here, TBCD is an essential factor for neuronal morphogenesis. Although specific human disorders caused by TBCD mutation have not been identified, human DSCAM is located in the Down syndrome critical region and is implicated in the cognitive disabilities seen in Down syndrome. We found that the gain-of-function phenotype of Dscam was suppressed by reduction in TBCD. Therefore, TBCD may contribute to structural alterations, functional alterations, or both of neural circuits in Down syndrome and other neurological disorders.

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    Epigallocatechin-3-gallate treatment to promote neuroprotection and functional recovery after nervous system injury
    Pere Boadas-Vaello, Enrique Verdú
    2015, 10 (9):  1390-1392.  doi: 10.4103/1673-5374.165502
    Abstract ( 186 )   PDF (514KB) ( 578 )   Save

    The epigallocatechin-3-gallate (EGCG) treatment may be a potential drug to promote neuroprotection and functional recovery after nervous system injury. However, additional experimental research will be necessary to further explore the biological mechanisms of this polyphenol in order to become a suitable and safe therapeutic treatment.

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    Repairing peripheral nerve injury using tissue engineering techniques
    Ernest W. Wang, Jun Zhang, Jason H. Huang
    2015, 10 (9):  1393-1394.  doi: 10.4103/1673-5374.165501
    Abstract ( 179 )   PDF (333KB) ( 807 )   Save

    With novel tissue engineering techniques, we hope that transplantation of these nervous tissue constructs will promote regeneration of transected nerves by providing a living pathway to guide host axons from the proximal nerve stump across nerve lesions with significant gaps. Thus, we hope to use our new technique to provide a significant advancement for major nerve reconstruction.

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    Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia
    Jenny A.K. Ekberg, James A. St John
    2015, 10 (9):  1395-1396.  doi: 10.4103/1673-5374.165504
    Abstract ( 197 )   PDF (273KB) ( 578 )   Save

    The therapeutic potential for OECs to repair the injured spinal cord is encouraging, however to clarify the efficacy of the therapy it is important that uniform and consistent purity of OECs are obtained. Considering that OECs from the peripheral nerve and from the olfactory bulb have distinctly different behavioural characteristics (Windus et al., 2010) it is clear that the different subpopulations can exert varying effects. When the potential inclusion of accessory OECs is also considered in animal models of spinal cord repair, their differing capacity for phagocytosis of axon debris will introduce another variable that will likely produce variable outcomes and confound the analysis of the therapeutic effect of OECs. Therefore, in order to achieve a more thorough understanding of the therapeutic potential of OECs and to achieve consistent outcomes in spinal injury models, it is crucial that strategies are developed to optimise the purification of the different subpopulations of OECs. As the accessory olfactory nerve bundles project along the septum and medial surfaces of the olfactory bulb, one simple strategy to minimise the potential contamination by the accessory OECs is to avoid harvesting cells from the septum/medial nerve fibre layer and instead harvest cells from the turbinates and lateral margins of the olfactory bulb. By improving the purity of the OEC preparations, we are likely to achieve more consistent outcomes in animal spinal injury models.

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    From adaption to death: endoplasmic reticulum stress as a novel target of selective neurodegeneration?
    Yiting Liu, James R. Connor
    2015, 10 (9):  1397-1398.  doi: 10.4103/1673-5374.165227
    Abstract ( 211 )   PDF (303KB) ( 623 )   Save

    Neurodegenerative disease is a condition in which subpopulations of neuronal cells of the brain and spinal cord are selectively lost. A common event in many neurodegenerative diseases, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis and prion diseases, is the increased level of endoplasmic reticulum (ER) stress caused by accumulation and deposits of inclusion bodies that contain abnormal aggregated proteins. However, the exact contributions to and causal effects of ER stress in neuron degeneration are not clear.
    The proper functioning of ER is critical for numerous aspects of cell physiology. Accordingly, the ability to respond to perturbations in ER function, called ER stress, is a fundamentally important property of all cells. ER stress includes the accumulation of unfolded, misfolded or excessive protein, alterations in calcium storage, ER lipid or glycolipid imbalances, or changes in the redox or ionic conditions of the ER lumen. The ER responds to the stressors by activating intracellular signal transduction pathways, collectively called the unfolded protein response (UPR). ER stress can be acute or chronic, chronic ER stress can be persistently tolerated for days to years, as in the case of neurodegenerative diseases, so that, even if some cell death occurs, the majority of cells will ultimately survive and adapt to the stress. Clearly, a better understanding and manipulation of the ER stress level could be beneficial in treating neurodegenerative diseases. In neurons limited ER stress could be tolerated, but still position the cells to be vulnerable to a physiological insult that is sub-lethal.

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    Tailoring of therapy for chronic inflammatory demyelinating polyneuropathy
    Yusuf A. Rajabally
    2015, 10 (9):  1399-1400.  doi: 10.4103/1673-5374.165594
    Abstract ( 258 )   PDF (492KB) ( 629 )   Save

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable immune-mediated disorder, which causes in its typical form, symmetric proximal and distal weakness with large fibre sensory impairment involving the four limbs. There are currently three main first-line therapeutic options for CIDP. These consist of corticosteroids, immunoglobulins and plasma exchanges (PE) which have all been found effective in a number of trials conducted over the past several years. No immunosuppressant therapy has shown benefit in CIDP, although they are utilized by many clinicians in various circumstances despite absence of an evidence base. CIDP is a heterogeneous entity and also consists of so-called “atypical forms”. These can be anatomical with focal and multifocal subtypes, or relate to the nerve fibre type involved, with pure sensory and pure motor variants. There are also forms co-existing with associated diseases. There are likely different pathophysiologic mechanisms for the different subtypes which may in turn affect best treatment to be offered for each variant. An example is the pure motor form of CIDP, for which there are a number of reports which have described deterioration on steroids, making immunoglobulins the favoured first-line treatment. The degree of electrophysiological, albeit asymptomatic, sensory involvement may hence also represent a marker of corticosteroid-responsiveness, as may also the degree of focal electrophysiological demyelination. Co-existing disease, such as diabetes may make use of certain treatments such as corticosteroids unadvisable.
    In conclusion, therapeutic decision-making in CIDP requires consideration of a number of different factors, relating principally to the individual patient’s circumstances. Disease severity, disease sub-type, age, comorbidities, all play a significant role in the process. First-line therapies most frequently suffice alone and in combination, and effects should be carefully evaluated using appropriate validated scales. Immunosuppressant treatment, although without an evidence base, should not be excluded in selected, albeit exceptional cases. The task of tailoring CIDP therapy for each patient is important, with often long-term implications. The right decision may not be easy but is crucial both in order to offer the maximum chances of remission and/or cure, while offering the justifiably most adequate therapeutic option for every affected individual in relation to risk exposure and side-effect profile.

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    Neuronal gene transcription modulates demyelination and remyelination in a mouse model of multiple sclerosis
    Sofia Anastasiadou, Bernd Knöll
    2015, 10 (9):  1401-1402.  doi: 10.4103/1673-5374.165507
    Abstract ( 289 )   PDF (492KB) ( 704 )   Save

    Additionally, our data emphasize the delicate balance of inflammation leading either to neurodegeneration or neuroprotection. Current therapeutic strategies for MS aim at suppressing CNS inflammation and enhancing neuroprotection. Therefore, molecular and cellular insights obtained in rodent MS models, highlighting the importance of the neuronal compartment for disease progression, might prove useful for the understanding of mechanisms involved in the onset of human MS disease. Finally, the investigation of neuronal signaling mechanisms, such as SRF mediated gene transcription, identified in MS mouse models, might provide new valuable molecular targets relevant to human MS therapy.

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    Substance P and its tachykinin NK1 receptor: a novel neuroprotective target for Parkinson’s disease
    Emma Thornton, Robert Vink
    2015, 10 (9):  1403-1405.  doi: 10.4103/1673-5374.165505
    Abstract ( 229 )   PDF (374KB) ( 651 )   Save

    Substance P-induced neurogenic inflammation may play an important role in the pathogenesis of Parkinson’s disease (PD), including L-DOPA induced dyskinesia (LID), by increasing BBB permeability and subsequent peripheral immune cell infiltration, as well as activation of resident immune cells. These injury cascades not only directly contribute to the ongoing neurodegeneration of dopaminergic neurons in PD but can also exacerbate other secondary injury mechanisms such as oxidative stress and mitochondrial dysfunction. Treatment with an NK1-R antagonist attenuated the progression of PD and significantly reduced the onset of LID, presumably by inhibiting multifactorial injury mechanisms involving SP and NK1-R. Blocking the effects of SP with a NK1-R antagonist therefore presents a potentially promising new avenue for neuroprotection in PD.

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    Application and implications of polyethylene glycol-fusion as a novel technology to repair injured spinal cords
    George D. Bittner, Kiran K. Rokkappanavar, Jean D. Peduzzi
    2015, 10 (9):  1406-1408.  doi: 10.4103/1673-5374.162772
    Abstract ( 245 )   PDF (236KB) ( 1849 )   Save
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    In search for novel strategies towards neuroprotection and neuroregeneration: is PPARα a promising therapeutic target?
    Sandra Moreno, Maria Paola Cerù
    2015, 10 (9):  1409-1412.  doi: 10.4103/1673-5374.165313
    Abstract ( 336 )   PDF (395KB) ( 628 )   Save

    In the early '90s, seminal work on rodent liver demonstrated that the hypolipidemic effect of xenobiotics, referred to as peroxisome proliferators, was mediated by a member of steroid hormone receptor superfamily, thus designated peroxisome proliferator-activated receptors (PPARs). The research field opened by this discovery led to the identification of three isotypes, namely PPARα (NR1C1), PPARβ/δ (NR1C2), PPARγ (NR1C3), in a wide range of tissues. All these receptors act as ligand-activated transcription factors, binding lipid molecules with different, though overlapping, specificity. PPARs, as other members of the nuclear receptor superfamily, comprise four domains - one of which binds to specific DNA sequences (PPAR response elements, PPREs) - regulating gene expression as heterodimers with retinoid X receptors (RXRs). PPAR activity is modulated by post-translational modifications, such as phosphorylation, SUMOylation, ubiquitylation, and by several corepressors and coactivators. It is now well established that PPARs act as lipid sensors, playing a major role in energy homeostasis, lipid metabolism and ROS production/scavenging, thus being involved in key cell processes, including cell proliferation, death and differentiation. These receptors are regulators of oxidative stress, inflammation and immune response, making them a suitable target for the treatment of chronic inflammatory diseases, diabetes, cancer and neurodegenerative disorders.90年代早期,在啮齿动物肝脏中的开创性工作证明了异生素的降血脂作用,即过氧化物酶体增殖是由类固醇激素受体超家族成员介导的,因而出现了过氧化物酶体增殖物激活受体(PPARs)。这一研究领域的发现引出了三个同种型受体,即PPARα(NR1C1),PPARβ/δ(NR1C2),PPARγ(NR1C3)。所有这些受体均为充当配体活化的转录因子,结合不同的脂质分子虽有重叠但各具特异性。意大利罗马第三大学Sandra Moreno教授在发表于《中国神经再生研究(英文版)》杂志2015年9月第9期的观点文章中主要介绍了PPARs——核受体超家族的其他成员,PPAR活性是通过转译后修饰的,如磷酸化,SUMO化,泛素化调制,以及由几个辅阻遏物的共激活因子。现在公认的是PPARs可作为脂质传感器,在能量稳态,脂质代谢和ROS产生/清除中起到主要作用,也因此被卷入关键细胞过程,包括细胞增殖,死亡和分化。这些受体是氧化应激,炎症和免疫反应的调节因素,并使之成为一个用于治疗慢性炎症疾病,糖尿病,癌症和神经退行性疾病治疗的合适靶标。Article: "In search for novel strategies towards neuroprotection and neuroregeneration: is PPARα a promising therapeutic target?" by Sandra Moreno1, Maria Paola Cerù1,2 (1 Department of Science-LIME, University Roma Tre, Rome, Italy 2 Department of Life, Health and Environmental Sciences, University of L’Aquila, Coppito (AQ), Italy). Moreno S, Cerù MP (2015) In search for novel strategies towards neuroprotection and neuroregeneration: is PPARα a promising therapeutic target? Neural Regen Res 10(9):1409-1412. 欲获更多资讯:请与《中国神经再生研究(英文版)》杂志国际发展部联络;联络电话:+8613804998773,或用电子邮件联络:eic@nrren.org。 文章全文请见:http://www.nrronline.org/

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    Is hyperexcitability really guilty in amyotrophic lateral sclerosis?
    Felix Leroy, Daniel Zytnicki
    2015, 10 (9):  1413-1415.  doi: 10.4103/1673-5374.165308
    Abstract ( 209 )   PDF (299KB) ( 582 )   Save

    Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of brainstem and spinal motoneurons as well as lateral cortico-spinal tracts. The onset generally occurs during the adult age except for some juvenile aggressive forms. Until recently, the vast majority of the cases (90%) were deemed sporadic. Mutations in the SOD1 gene have been for a long time the only ones reported in familiar forms of ALS. The recent implication of new genes of little known function cast a new view on this disease. C9ORF75, for example, is now recognized to account for 30% of the familial cases. Overall, ALS has been linked to 20 different genes, many also associated with other degenerative diseases (frontotemporal dementia, Alzheimer or ataxia). Some of these genes are involved in RNA maturation (FUS, TARBD). Clinical observation of human patients and mouse models suggest that all motor pools and motoneurons are not equally affected. The disease usually starts in motor pools controlling the limbs or in the bulbar area before expanding to other motor pools, with the exception of a few resistant ones (Onuf’s and oculomotor nuclei). Within a vulnerable motor pool, motoneurons subtypes also exhibit differential vulnerability and follow an orderly degeneration; starting with the motoneurons innervating fast-contracting fatigable motor units (FF motoneurons) and followed by the ones innervating fast-contractile fatigue-resistant motor units (FR motoneurons). The motoneurons innervating slow motor units (S motoneurons) appear resistant to the disease. Although the mechanisms leading to the orderly degeneration are not known, many hypotheses have been raised.

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    ubaxial cervical spine injury classification system: is it most appropriate for classifying cervical injury?
    Rafael Martínez-Pérez, Francisco Fuentes, Víctor S. Alemany
    2015, 10 (9):  1416-1417.  doi: 10.4103/1673-5374.165508
    Abstract ( 360 )   PDF (146KB) ( 1794 )   Save

    “Classical” cervical injury classifications are characterized for its complexity, low applicability, and its uselessness in guiding therapeutic options. New schemes, as SLIC system, include determinant factors in prognosis, such as neurological impairment. It will hopefully facilitate the development of evidence-based guidelines that may influence other aspects of the therapeutic decision-making process (eg., which operative approach is most appropriate for a particular injury). We certainly believe its accuracy and reproducibility will increase over time as surgeons become more familiar with the protocol.

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    Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a “brake” on neuronal excitability in ischemic stroke
    Pallab Bhattacharya, Anand Kumar Pandey, Sudip Paul, Ranjana Patnaik
    2015, 10 (9):  1418-1420.  doi: 10.4103/1673-5374.165509
    Abstract ( 269 )   PDF (546KB) ( 629 )   Save

    Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA) in rodent’s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA). This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

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    Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke
    Feng Yan, Wei Yue, Yue-lin Zhang, Guo-chao Mao, Ke Gao, Zhen-xing Zuo, Ya-jing Zhang, Hui Lu
    2015, 10 (9):  1421-1426.  doi: 10.4103/1673-5374.163466
    Abstract ( 181 )   PDF (1489KB) ( 905 )   Save

    In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hitosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the ischemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-specific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

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    Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression
    Hao-hao Chen1, Ning Zhang, Wei-yun Li, Ma-rong Fang, Hui Zhang, Yuan-shu Fang, Ming-xing Ding, Xiao-yan Fu
    2015, 10 (9):  1427-1432.  doi: 10.4103/1673-5374.165510
    Abstract ( 153 )   PDF (966KB) ( 898 )   Save

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. A BDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippocampus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open field test in these rats as well. These findings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

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    Oxygen-glucose deprivation regulates BACE1 expression through induction of autophagy in Neuro-2a/APP695 cells
    Rong-fu Chen, Ting Zhang, Yin-yi Sun, Ya-meng Sun, Wen-qi Chen, Nan Shi, Fang Shen, Yan Zhang, Kang-yong Liu, Xiao-jiang Sun
    2015, 10 (9):  1433-1440.  doi: 10.4103/1673-5374.165511
    Abstract ( 177 )   PDF (1389KB) ( 846 )   Save

    Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide (Aβ) in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 (APP695) cell models of cerebral ischemia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin (an autophagy inducer) or 3-methyladenine (an autophagy inhibitor) on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.

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    The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia
    Ya-yun Yan, Xiao-ming Wang, Yan Jiang, Han Chen, Jin-ting He, Jing Mang, Yan-kun Shao*, Zhong-xin Xu*
    2015, 10 (9):  1441-1449.  doi: 10.4103/1673-5374.165512
    Abstract ( 171 )   PDF (3316KB) ( 737 )   Save

    The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intragastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its related protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These findings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemia via the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.

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    Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion
    Xu He, Feng-jun Deng, Jin-wen Ge, Xiao-xin Yan, Ai-hua Pan, Zhi-yuan Li
    2015, 10 (9):  1450-1456.  doi: 10.4103/1673-5374.165514
    Abstract ( 187 )   PDF (2480KB) ( 930 )   Save

    The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood flow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total saponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of doublecortin (DCX)+ neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These findings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

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    Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy
    Nan Yang, He Liu, Yao Jiang, Ji Zheng, Dong-mei Li, Chao Ji, Yan-yong Liu, Ping-ping Zuo
    2015, 10 (9):  1457-1462.  doi: 10.4103/1673-5374.165516
    Abstract ( 277 )   PDF (1234KB) ( 941 )   Save

    Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.

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    Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit
    Botond Gaal, Einar Örn Jóhannesson, Amit Dattani, Agnes Magyar, Ildikó Wéber, Clara Matesz
    2015, 10 (9):  1463-1470.  doi: 10.4103/1673-5374.165517
    Abstract ( 296 )   PDF (1895KB) ( 753 )   Save

    We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrinthectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestibular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tenascin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.

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    Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury
    Yan-bo Zhang, Zheng-dong Guo, Mei-yi Li, Si-jie Li, Jing-zhong Niu, Ming-feng Yang, Xun-ming Ji, Guo-wei Lv
    2015, 10 (9):  1471-1476.  doi: 10.4103/1673-5374.165519
    Abstract ( 222 )   PDF (1041KB) ( 723 )   Save

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats.

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    Chuan-gang Peng, Shu-quan Zhang, Min-fei Wu, Yang Lv, Dan-kai Wu, Qi Yang, Rui Gu
    2015, 10 (9):  1477-1482.  doi: 10.4103/1673-5374.165520
    Abstract ( 240 )   PDF (946KB) ( 989 )   Save
    null
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    Transplantation of erythropoietin gene-modified neural stem cells improves the repair of injured spinal cord
    Min-fei Wu, Shu-quan Zhang, Rui Gu, Jia-bei Liu, Ye Li, Qing-san Zhu
    2015, 10 (9):  1483-1490.  doi: 10.4103/1673-5374.165521
    Abstract ( 253 )   PDF (878KB) ( 768 )   Save

    The protective effects of erythropoietin on spinal cord injury have not been well described. Here, the eukaryotic expression plasmid pcDNA3.1 human erythropoietin was transfected into rat neural stem cells cultured in vitro. A rat model of spinal cord injury was established using a free falling object. In the human erythropoietin-neural stem cells group, transfected neural stem cells were injected into the rat subarachnoid cavity, while the neural stem cells group was injected with non-transfected neural stem cells. Dulbecco’s modified Eagle’s medium/F12 medium was injected into the rats in the spinal cord injury group as a control. At 1–4 weeks post injury, the motor function in the rat lower limbs was best in the human erythropoietin-neural stem cells group, followed by the neural stem cells group, and lastly the spinal cord injury group. At 72 hours, compared with the spinal cord injury group, the apoptotic index and Caspase-3 gene and protein expressions were apparently decreased, and the bcl-2 gene and protein expressions were noticeably increased, in the tissues surrounding the injured region in the human erythropoietin-neural stem cells group. At 4 weeks, the cavities were clearly smaller and the motor and somatosensory evoked potential latencies were remarkably shorter in the human erythropoietin-neural stem cells group and neural stem cells group than those in the spinal cord injury  group. These differences were particularly obvious in the human erythropoietin-neural stem cells group. More CM-Dil-positive cells and horseradish peroxidase-positive nerve fibers and larger amplitude motor and somatosensory evoked potentials were found in the human erythropoietin-neural stem cells group and neural stem cells group than in the spinal cord injury group. Again, these differences were particularly obvious in the human erythropoietin-neural stem cells group. These data indicate that transplantation of erythropoietin gene-modified neural stem cells into the subarachnoid cavity to help repair spinal cord injury and promote the recovery of spinal cord function better than neural stem cell transplantation alone. These findings may lead to significant improvements in the clinical treatment of spinal cord injuries.

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    Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury
    Qun Zhao, Zhi-yue Li, Ze-peng Zhang, Zhou-yun Mo, Shi-jie Chen, Si-yu Xiang, Qing-shan Zhang, Min Xue
    2015, 10 (9):  1491-1497.  doi: 10.4103/1673-5374.165522
    Abstract ( 195 )   PDF (642KB) ( 601 )   Save

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

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    Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells
    Yan-ru Zhang, Ka Ka, Ge-chen Zhang, Hui Zhang, Yan Shang, Guo-qiang Zhao, Wen-hua Huang
    2015, 10 (9):  1498-1506.  doi: 10.4103/1673-5374.165523
    Abstract ( 236 )   PDF (1434KB) ( 723 )   Save

    Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic factor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when allografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury.

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    Stem Cell Ophthalmology Treatment Study (SCOTS) for retinal and optic nerve diseases: a case report of improvement in relapsing auto-immune optic neuropathy
    Jeffrey N. Weiss, Steven Levy, Susan C. Benes
    2015, 10 (9):  1507-1515.  doi: 10.4103/1673-5374.165525
    Abstract ( 362 )   PDF (2713KB) ( 1088 )   Save

    We present the results from a patient with relapsing optic neuropathy treated within the Stem Cell Ophthalmology Treatment Study (SCOTS). SCOTS is an Institutional Review Board approved clinical trial and has become the largest ophthalmology stem cell study registered at the National Institutes of Health to date (www.clinicaltrials.gov Identifier NCT 01920867). SCOTS utilizes autologous bone marrow-derived stem cells (BMSCs) for treatment of retinal and optic nerve diseases. Pre-treatment and post-treatment comprehensive eye exams of a 54 year old female patient were performed both at the Florida Study Center, USA and at The Eye Center of Columbus, USA. As a consequence of a relapsing optic neuritis, the patient’s previously normal visual acuity decreased to between 20/350 and 20/400 in the right eye and to 20/70 in the left eye. Significant visual field loss developed bilaterally. The patient underwent a right eye vitrectomy with injection of BMSCs into the optic nerve of the right eyeand retrobulbar, subtenon and intravitreal injection of BMSCs in the left eye. At 15 months after SCOTS treatment, the patient’s visual acuity had improved to 20/150 in the right eye and 20/20 in the left eye. Bilateral visual fields improved markedly. Both macular thickness and fast retinal nerve fiber layer thickness were maximally improved at 3 and 6 months after SCOTS treatment. The patient also reduced her mycophenylate dose from 1,500 mg per day to 500 mg per day and required no steroid pulse therapy during the 15-month follow up.

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    Optimal concentration and time window for proliferation and differentiation of neural stem cells from embryonic cerebral cortex: 5% oxygen preconditioning for 72 hours
    Li-li Yuan, Ying-jun Guan, Deng-dian Ma, Hong-mei Du
    2015, 10 (9):  1516-1522.  doi: 10.4103/1673-5374.165526
    Abstract ( 179 )   PDF (979KB) ( 784 )   Save

    Hypoxia promotes proliferation and differentiation of neural stem cells from embryonic day 12 rat brain tissue, but the concentration and time of hypoxic preconditioning are controversial. To address this, we cultured neural stem cells isolated from embryonic day 14 rat cerebral cortex in 5% and 10% oxygen in vitro. MTT assay, neurosphere number, and immunofluorescent staining found that 5% or 10% oxygen preconditioning for 72 hours improved neural stem cell viability and proliferation. With prolonged hypoxic duration (120 hours), the proportion of apoptotic cells increased. Thus, 5% oxygen preconditioning for 72 hours promotes neural stem cell proliferation and neuronal differentiation. Our findings indicate that the optimal concentration and duration of hypoxic preconditioning for promoting proliferation and differentiation of neural stem cells from the cerebral cortex are 5% oxygen for 72 hours.

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    Elastic modulus affects the growth and differentiation of neural stem cells
    Xian-feng Jian, Kai Yang, Xiao-qing Yang, Ying-fu Liu, Yuan-chi Cheng, Xu-yi Chen, Yue Tu
    2015, 10 (9):  1523-1527.  doi: 10.4103/1673-5374.165527
    Abstract ( 316 )   PDF (1268KB) ( 835 )   Save

    It remains poorly understood if carrier hardness, elastic modulus, and contact area affect neural stem cell growth and differentiation. Tensile tests show that the elastic moduli of Tiansu and SMI silicone membranes are lower than that of an ordinary dish, while the elastic modulus of SMI silicone membrane is lower than that of Tiansu silicone membrane. Neural stem cells from the cerebral cortex of embryonic day 16 Sprague-Dawley rats were seeded onto ordinary dishes as well as Tiansu silicone membrane and SMI silicone membrane. Light microscopy showed that neural stem cells on all three carriers show improved adherence. After 7 days of differentiation, neuron specific enolase, glial fibrillary acidic protein, and myelin basic protein expression was detected by immunofluorescence. Moreover, flow cytometry revealed a higher rate of neural stem cell differentiation into astrocytes on Tiansu and SMI silicone membranes than on the ordinary dish, which was also higher on the SMI than the Tiansu silicone membrane. These findings confirm that all three cell carrier types have good biocompatibility, while SMI and Tiansu silicone membranes exhibit good mechanical homogenization. Thus, elastic modulus affects neural stem cell differentiation into various nerve cells. Within a certain range, a smaller elastic modulus results in a more obvious trend of cell differentiation into astrocytes. 

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    Is transcranial magnetic stimulation useful in posttraumatic disorders?
    Wellingson Silva Paiva, Iuri Santana Neville, Felipe Fregni, Manoel Jacobsen Teixeira
    2015, 10 (9):  1528-1528.  doi: 10.4103/1673-5374.165529
    Abstract ( 212 )   PDF (128KB) ( 645 )   Save
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