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    22 August 2014, Volume 9 Issue 16 Previous Issue    Next Issue
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    Cervical spinal cord injury: tailoring clinical trial endpoints to reflect meaningful functional improvements
    Lisa M. Bond, Lisa McKerracher
    2014, 9 (16):  1493-1497.  doi: 10.4103/1673-5374.139470
    Abstract ( 239 )   PDF (329KB) ( 741 )   Save

    Cervical spinal cord injury (SCI) results in partial to full paralysis of the upper and lower extremities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control (e.g., upper extremity motor score, motor level change) show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement.

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    Peripheral nerve lengthening as a regenerative strategy
    Kenneth M. Vaz, Justin M. Brown, Sameer B. Shah
    2014, 9 (16):  1498-1501.  doi: 10.4103/1673-5374.139471
    Abstract ( 218 )   PDF (470KB) ( 711 )   Save

    Peripheral nerve injury impairs motor, sensory, and autonomic function, incurring substantial financial costs and diminished quality of life. For large nerve gaps, proximal lesions, or chronic nerve injury, the prognosis for recovery is particularly poor, even with autografts, the current gold standard for treating small to moderate nerve gaps. In vivo elongation of intact proximal stumps towards the injured distal stumps of severed peripheral nerves may offer a promising new strategy to treat nerve injury. This review describes several nerve lengthening strategies, including a novel internal fixator device that enables rapid and distal reconnection of proximal and distal nerve stumps.

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    Efficacy of granulocyte-colony stimulating factor treatment in a rat model of anterior ischemic optic neuropathy
    Shun-Ping Huang, Rong-Kung Tsai
    2014, 9 (16):  1502-1505.  doi: 10.4103/1673-5374.139472
    Abstract ( 222 )   PDF (285KB) ( 709 )   Save

    Non-arteritic anterior ischemic optic neuropathy (NA-AION) is the most common cause of acute ischemic damage to the optic nerve (ON), and the leading cause of seriously impaired vision in people over 55 years of age. It demonstrated that subcutaneous administration of Granulocyte colony-stimulating factor (G-CSF) reduces RGC death in an ON crush model in rats, and that the neuroprotective effects may involve both anti-apoptotic and anti-inflammatory processes. Our recent work shows that the protective actions of G-CSF in rAION models may involve both anti-apoptotic and anti-inflammatory processes. However, the exact rescuing mechanisms involved in the administration of G-CSF in rAION models need further investigation. In addition, further studies on the administration of G-CSF at different time intervals after the induction of rAION may be able to illustrate whether treatment given at a later time is still neuroprotective. Further, it is unknown whether treatment using G-CSF combined with other drugs will result in a synergistic effect in a rAION model. Inflammation induced by ischemia plays an essential role on the ON head in NA-AION, which can result in disc edema and compartment changes. Therefore, it is reasonable that adding an anti-inflammatory drug may enhance the therapeutic effects of G-CSF. An ongoing goal is to evaluate the novel sites of action of both G-CSF and other anti-inflammatory drugs, and to identify the functionally protective pathways to enhance RGC survival. These investigations may open up new therapeutic avenues for the treatment of ischemic optic neuropathy.

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    The biochemical pathways of central nervous system neural degeneration in niacin deficiency
    Linshan Fu, Venkatesh Doreswamy, Ravi Prakash
    2014, 9 (16):  1509-1513.  doi: 10.4103/1673-5374.139475
    Abstract ( 234 )   PDF (193KB) ( 1109 )   Save

    Neural degeneration is a very complicated process. In spite of all the advancements in the molecular chemistry, there are many unknown aspects of the phenomena of neurodegeneration which need to be put together. It is a common sequela of the conditions of niacin deficiency.  Neural degeneration in Pellagra manifests as chromatolysis mainly in pyramidal followed by other neurons and glial cells. However, there is a gross lack of understanding of biochemical mechanisms of neurodegeneration in niacin deficiency states. Because of the necessity of niacin or its amide derivative NAD in a number of biochemical pathways, it is understandable that several of these pathways may be involved in the common outcome of neural degeneration. Here, we highlight five pathways that could be involved in the neuraldegeneration for which evidence has accumulated through several studies. These pathways are: 1) the tryptophan-kyneurenic acid pathway, 2) the mitochondrial ATP generation related pathways, 3) the poly (ADP-ibose) polymerase (PARP) pathway, 4) the BDNF-TRKB Axis abnormalities, 5) the genetic influences of niacin deficiency.

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    Effects of naringin, a flavanone glycoside in grapefruits and citrus fruits, on the nigrostriatal dopaminergic projection in the adult brain
    Un Ju Jung, Sang Ryong Kim
    2014, 9 (16):  1514-1517.  doi: 10.4103/1673-5374.139476
    Abstract ( 288 )   PDF (256KB) ( 1005 )   Save

    Recently, we have demonstrated the ability of naringin, a well-known flavanone glycoside of grapefruits and citrus fruits, to prevent neurodegeneration in a neurotoxin model of Parkinson’s disease. Intraperitoneal injection of naringin protected the nigrostriatal dopaminergic projection by increasing glial cell line-derived neurotrophic factor expression and decreasing the level of tumor necrosis factor-alpha in dopaminergic neurons and microglia, respectively. These results suggest that naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson’s disease with anti-inflammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson’s disease.

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    Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury
    Yuzhen Dong, Libin Yang, Lin Yang, Hongxing Zhao, Chao Zhang, Dapeng Wu
    2014, 9 (16):  1520-1524.  doi: 10.4103/1673-5374.139478
    Abstract ( 228 )   PDF (217KB) ( 629 )   Save

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

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    Acrylamide inhibits nerve sprouting induced by botulinum toxin type A
    Hong Jiang, Yi Xiang, Xingyue Hu, Huaying Cai
    2014, 9 (16):  1525-1531.  doi: 10.4103/1673-5374.139479
    Abstract ( 269 )   PDF (217KB) ( 650 )   Save

    Botulinum toxin type A is a potent muscle relaxant that blocks the transmission and release of acetylcholine at the neuromuscular junction. Intramuscular injection of botulinum toxin type A has served as an effective and safe therapy for strabismus and focal dystonia. However, muscular weakness is temporary and after 3–4 months, muscle strength usually recovers because functional recovery is mediated by nerve sprouting and reconstruction of the neuromuscular junction. Acrylamide may produce neurotoxic substances that cause retrograde necrotizing neuropathy and inhibit nerve sprouting caused by botulinum toxin type A. This study investigated whether acrylamide inhibits nerve sprouting after intramuscular injection of botulinum toxin type A. A tibial nerve sprouting model was established through local injection of botulinum toxin type A into the right gastrocnemius muscle of Sprague-Dawley rats. Following intramuscular injection, rats were given intraperitoneal injection of 3% acrylamide every 3 days for 21 days. Nerve sprouting appeared 2 weeks after intramuscular injection of botulinum toxin type A and single-fiber electromyography revealed abnormal conduction at the neuromuscular junction 1 week after intramuscular injection of botulinum toxin type A. Following intraperitoneal injection of acrylamide, the peak muscle fiber density decreased. Electromyography jitter value were restored to normal levels 6 weeks after injection. This indicates that the maximal decrease in fiber density and the time at which functional conduction of neuromuscular junction was restored were delayed. Additionally, the increase in tibial nerve fibers was reduced. Acrylamide inhibits nerve sprouting caused by botulinum toxin type A and may be used to prolong the clinical dosage of botulinum toxin type A.

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    Cutaneous sensory nerve as a substitute for auditory nerve in solving deaf-mutes’ hearing problem: an innovation in multi-channel-array skin-hearing technology
    Jianwen Li, Yan Li, Ming Zhang, Weifang Ma, Xuezong Ma
    2014, 9 (16):  1532-1540.  doi: 10.4103/1673-5374.139480
    Abstract ( 242 )   PDF (1639KB) ( 670 )   Save

    The current use of hearing aids and artificial cochleas for deaf-mute individuals depends on their auditory nerve. Skin-hearing technology, a patented system developed by our group, uses a cutaneous sensory nerve to substitute for the auditory nerve to help deaf-mutes to hear sound. This paper introduces a new solution, multi-channel-array skin-hearing technology, to solve the problem of speech discrimination. Based on the filtering principle of hair cells, external voice signals at different frequencies are converted to current signals at corresponding frequencies using electronic multi-channel bandpass filtering technology. Different positions on the skin can be stimulated by the electrode array, allowing the perception and discrimination of external speech signals to be determined by the skin response to the current signals. Through voice frequency analysis, the frequency range of the band-pass filter can also be determined. These findings demonstrate that the sensory nerves in the skin can help to transfer the voice signal and to distinguish the speech signal, suggesting that the skin sensory nerves are good candidates for the replacement of the auditory nerve in addressing deaf-mutes’ hearing problems. Scientific hearing experiments can be more safely performed on the skin. Compared with the artificial cochlea, multi-channel-array skin-hearing aids have lower operation risk in use, are cheaper and are more easily popularized.

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     T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer’s disease mice
    Jing Liu, Yuxin Ma, Sumin Tian, Li Zhang, Mengmeng Zhao, Yaqiong Zhang, Dachuan Xu
    2014, 9 (16):  1541-1547.  doi: 10.4103/1673-5374.139481
    Abstract ( 306 )   PDF (767KB) ( 1123 )   Save

    Alzheimer’s disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1–42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeficiency to establish an animal model of Alzheimer’s disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was significantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines (interleukin-2, interferon-γ) and hippocampal microglia-related cytokines (interleukin-1β, tumor necrosis factor-α) correlated with the number of regenerated neural progenitor cells in the hippocampus. These results indicate that T cells promote hippocampal neurogenesis in Alzheimer’s disease and T-cell immunodeficiency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer’s disease mice. Our findings provide an experimental basis for understanding the role of T cells in Alzheimer’s disease.

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    Brain structural changes and their correlation with vascular disease in type 2 diabetes mellitus patients: a voxel-based morphometric study
    Chunxia Wang, Kailiang Fu, Huaijun Liu, Fei Xing, Songyun Zhang
    2014, 9 (16):  1548-1556.  doi: 10.4103/1673-5374.139482
    Abstract ( 170 )   PDF (1124KB) ( 823 )   Save

    Voxel-based morphometry has been used in the study of alterations in brain structure in type 1 diabetes mellitus patients. These changes are associated with clinical indices. The age at onset, pathogenesis, and treatment of type 1 diabetes mellitus are different from those for type 2 diabetes mellitus. Thus, type 1 and type 2 diabetes mellitus may have different impacts on brain structure. Only a few studies of the alterations in brain structure in type 2 diabetes mellitus patients using voxel-based morphometry have been conducted, with inconsistent results. We detected subtle changes in the brain structure of 23 cases of type 2 diabetes mellitus, and demonstrated that there was no significant difference between the total volume of gray and white matter of the brain of type 2 diabetes mellitus patients and that in controls. Regional atrophy of gray matter mainly occurred in the right temporal and left occipital cortex, while regional atrophy of white matter involved the right temporal lobe and the right cerebellar hemisphere. The ankle-brachial index in patients with type 2 diabetes mellitus strongly correlated with the volume of brain regions in the default mode network. The ankle-brachial index, followed by the level of glycosylated hemoglobin, most strongly correlated with the volume of gray matter in the right temporal lobe. These data suggest that voxel-based morphometry could detect small structural changes in patients with type 2 diabetes mellitus. Early macrovascular atherosclerosis may play a crucial role in subtle brain atrophy in type 2 diabetes mellitus patients, with chronic hyperglycemia playing a lesser role.

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    Neuroprotective effects of berry fruits on neurodegenerative diseases
    Selvaraju Subash, Musthafa Mohamed Essa, Samir Al-Adawi, Mushtaq A. Memon, Thamilarasan Manivasagam, Mohammed Akbar
    2014, 9 (16):  1557-1566.  doi: 10.4103/1673-5374.139483
    Abstract ( 204 )   PDF (467KB) ( 1395 )   Save

    Recent clinical research has demonstrated that berry fruits can prevent age-related neurodegenerative diseases and improve motor and cognitive functions. The berry fruits are also capable of modulating signaling pathways involved in inflammation, cell survival, neurotransmission and enhancing neuroplasticity. The neuroprotective effects of berry fruits on neurodegenerative diseases are related to phytochemicals such as anthocyanin, caffeic acid, catechin, quercetin, kaempferol and tannin. In this review, we made an attempt to clearly describe the beneficial effects of various types of berries as promising neuroprotective agents.

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    Telemedicine and digital management in repair and regeneration after nerve injury and in nervous system diseases
    Weijun Zhu, Yunkai Zhai, Dongxu Sun, Jie Zhao
    2014, 9 (16):  1567-1568.  doi: 10.4103/1673-5374.139484
    Abstract ( 207 )   PDF (127KB) ( 605 )   Save
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