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    30 June 2016, Volume 11 Issue 6 Previous Issue    Next Issue
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    Endogenous bioelectric fields: a putative regulator of wound repair and regeneration in the central nervous system
    Matthew L. Baer, Raymond J. Colello
    2016, 11 (6):  861-864.  doi: 10.4103/1673-5374.184446
    Abstract ( 165 )   PDF (509KB) ( 444 )   Save

    Studies on a variety of highly regenerative tissues, including the central nervous system (CNS) in non-mammalian vertebrates, have consistently demonstrated that tissue damage induces the formation of an ionic current at the site of injury. These injury currents generate electric fields (EF) that are 100-fold increased in intensity over that measured for uninjured tissue. In vitro and in vivo experiments have convincingly demonstrated that these electric fields (by their orientation, intensity and duration) can drive the migration, proliferation and differentiation of a host of cell types. These cellular behaviors are all necessary to facilitate regeneration as blocking these EFs at the site of injury inhibits tissue repair while enhancing their intensity promotes repair. Consequently, injury-induced currents, and the EFs they produce, represent a potent and crucial signal to drive tissue regeneration and repair. In this review, we will discuss how injury currents are generated, how cells detect these currents and what cellular responses they can induce. Additionally, we will describe the growing evidence suggesting that EFs play a key role in regulating the cellular response to injury and may be a therapeutic target for inducing regeneration in the mammalian CNS.

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    Neuroprotection and antioxidants
    Maria Lalkovičová, Viera Danielisová
    2016, 11 (6):  865-874.  doi: 10.4103/1673-5374.184447
    Abstract ( 162 )   PDF (583KB) ( 475 )   Save

    Ischemia as a serious neurodegenerative disorder causes together with reperfusion injury many changes in nervous tissue. Most of the neuronal damage is caused by complex of biochemical reactions and substantial processes, such as protein agregation, reactions of free radicals, insufficient blood supply, glutamate excitotoxicity, and oxidative stress. The result of these processes can be apoptotic or necrotic cell death and it can lead to an irreversible damage. Therefore, neuroprotection and prevention of the neurodegeneration are highly important topics to study. There are several approaches to prevent the ischemic damage. Use of many modern therapeutical methods and the incorporation of several substances into the diet of patients is possible to stimulate the endogenous protective mechanisms and improve the life quality.

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    The intricacies of neurotrophic factor therapy for retinal ganglion cell rescue in glaucoma: a case for gene therapy
    Marianna Foldvari, Ding Wen Chen
    2016, 11 (6):  875-877.  doi: 10.4103/1673-5374.184448
    Abstract ( 224 )   PDF (336KB) ( 429 )   Save

    Regeneration of damaged retinal ganglion cells (RGC) and their axons is an important aspect of reversing vision loss in glaucoma patients. While current therapies can effectively lower intraocular pressure, they do not provide extrinsic support to RGCs to actively aid in their protection and regeneration. The unmet need could be addressed by neurotrophic factor gene therapy, where plasmid DNA, encoding neurotrophic factors, is delivered to retinal cells to maintain sufficient levels of neurotrophins in the retina. In this review, we aim to describe the intricacies in the design of the therapy including: the choice of neurotrophic factor, the site and route of administration and target cell populations for gene delivery. Furthermore, we also discuss the challenges currently being faced in RGC-related therapy development with special considerations to the existence of multiple RGC subtypes and the lack of efficient and representative in vitro models for rapid and reliable screening in the drug development process.

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    Discovery of nigral dopaminergic neurogenesis in adult mice
    Brad E. Morrison
    2016, 11 (6):  878-881.  doi: 10.4103/1673-5374.184449
    Abstract ( 115 )   PDF (336KB) ( 416 )   Save

    Parkinson’s disease is characterized by the loss of dopaminergic neurons in the substantia nigra. As a result, intensive efforts have focused upon mechanisms that facilitate the death of mature dopaminergic neurons. Unfortunately, these efforts have been unsuccessful in providing an effective treatment to address neurodegeneration in this disease. Therefore, alternative theories of pathogenesis are being explored. Adult neurogenesis of dopaminergic neurons is an attractive concept that would provide a possible mechanism of neurodegeneration as well as offer an endogenous means to replenish affected neurons. To determine whether dopaminergic neurons experience neurogenesis in adult mice we developed a novel cell lineage tracing model that permitted detection of neurogenesis without many of the issues associated with popular techniques. Remarkably, we discovered that dopaminergic neurons are replenished in adult mice by Nestin+/Sox2- progenitor cells. What’s more, the rate of neurogenesis is similar to the rate of dopaminergic neuron loss reported using a chronic, systemic inflammatory response mouse model. This observation may indicate that neuron loss in Parkinson’s disease results from inhibition of neurogenesis.

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    Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate
    Christian A. Bowers, Bornali Kundu, Gregory W. J. Hawryluk
    2016, 11 (6):  882-885.  doi: 10.4103/1673-5374.184450
    Abstract ( 299 )   PDF (445KB) ( 897 )   Save

    Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS’s status as a historical standard of care.

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    Oligodendrocyte ablation as a tool to study demyelinating diseases
    Ahdeah Pajoohesh-Ganji, Robert H. Miller
    2016, 11 (6):  886-889.  doi: 10.4103/1673-5374.184451
    Abstract ( 216 )   PDF (1505KB) ( 679 )   Save

    Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation.

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    Oligodendrocyte ablation as a tool to study demyelinating diseases Role of myelin auto-antigens in pain: a female connection
    Veronica I. Shubayev, Alex Y. Strongin, Tony L. Yaksh
    2016, 11 (6):  890-891.  doi: 10.4103/1673-5374.184452
    Abstract ( 268 )   PDF (272KB) ( 443 )   Save
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    Bursting the unfolded protein response accelerates axonal regeneration
    Maritza Oñate, Felipe A. Court, Claudio Hetz
    2016, 11 (6):  892-893.  doi: 10.4103/1673-5374.184453
    Abstract ( 250 )   PDF (399KB) ( 666 )   Save
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    Graphene platform for neural regenerative medicine
    Tasneem Bouzid, Alexander Sinitskii, Jung Yul Lim
    2016, 11 (6):  894-895.  doi: 10.4103/1673-5374.184454
    Abstract ( 198 )   PDF (540KB) ( 602 )   Save
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    Neuroprotective role of galectin-1 in central nervous system pathophysiology
    Ravikumar Aalinkeel, Supriya D. Mahajan
    2016, 11 (6):  896-897.  doi: 10.4103/1673-5374.184455
    Abstract ( 236 )   PDF (295KB) ( 465 )   Save
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    N-acetyl proline-glycine-proline: implications for neurological disorders
    Jeff W. Hill, Edwin M. Nemoto
    2016, 11 (6):  898-899.  doi: 10.4103/1673-5374.184478
    Abstract ( 330 )   PDF (310KB) ( 423 )   Save
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    Role of granulocyte macrophage colony stimulating factor in regeneration of the central nervous system
    Ushananthini Shanmugalingam, Nafisa M. Jadavji, Patrice D. Smith
    2016, 11 (6):  902-903.  doi: 10.4103/1673-5374.184479
    Abstract ( 270 )   PDF (422KB) ( 527 )   Save
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    Neuroprotective properties of extracellular vesicles derived from mesenchymal stem cells
    Akvilė Jarmalavičiūtė, Augustas Pivoriūnas
    2016, 11 (6):  904-905.  doi: 10.4103/1673-5374.184480
    Abstract ( 227 )   PDF (182KB) ( 650 )   Save
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    The role of postsynaptic density proteins in neural degeneration and regeneration
    Yukti Vyas, Johanna M. Montgomery
    2016, 11 (6):  906-907.  doi: 10.4103/1673-5374.184481
    Abstract ( 231 )   PDF (307KB) ( 458 )   Save
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    Targeting BPOZ-2 in Lewy body disease
    Avik Roy
    2016, 11 (6):  910-911.  doi: 10.4103/1673-5374.184483
    Abstract ( 241 )   PDF (494KB) ( 427 )   Save
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    ARBs improve stroke outcome through an AT2-dependent, BDNF-induced proangiogenic and prorecovery response
    Ahmed Alhusban, Abdelrahman Y. Fouda, Susan C. Fagan
    2016, 11 (6):  912-913.  doi: 10.4103/1673-5374.184484
    Abstract ( 145 )   PDF (288KB) ( 446 )   Save
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    Time dependent differences in gray matter volume post mild traumatic brain injury
    Prabhjyot Singh, William D. S. Killgore
    2016, 11 (6):  920-921.  doi: 10.4103/1673-5374.184487
    Abstract ( 148 )   PDF (307KB) ( 364 )   Save
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    Decorin treatment for reversing trabecular meshwork fibrosis in open-angle glaucoma
    Lisa J Hill, Zubair Ahmed, Ann Logan
    2016, 11 (6):  922-923.  doi: 10.4103/1673-5374.184489
    Abstract ( 154 )   PDF (177KB) ( 1462 )   Save
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    Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia
    Dae Young Yoo, Ki-Yeon Yoo, Joon Ha Park, Hyun Jung Kwon, Hyo Young Jung, Jong Whi Kim, Goang-Min Choi, Seung Myung Moon, Dae Won Kim, Yeo Sung Yoon, Moo-Ho Won, In Koo Hwang
    2016, 11 (6):  924-930.  doi: 10.4103/1673-5374.184490
    Abstract ( 212 )   PDF (2734KB) ( 619 )   Save

    In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H), and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1–2 days and then increased once again within the CA1 region at 4–7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4–7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

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    Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury
    Yue Tu, Xiao-mei Miao, Tai-long Yi, Xu-yi Chen, Hong-tao Sun, Shi-xiang Cheng, Sai Zhang
    2016, 11 (6):  931-936.  doi: 10.4103/1673-5374.184491
    Abstract ( 302 )   PDF (2414KB) ( 700 )   Save

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and bloodbrain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury.

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    Developmental process of the arcuate fasciculus from infancy to adolescence: a diffusion tensor imaging study
    Hyeong Jun Tak, Jin Hyun Kim, Su Min Son
    2016, 11 (6):  937-943.  doi: 10.4103/1673-5374.184492
    Abstract ( 494 )   PDF (545KB) ( 620 )   Save

    We investigated the radiologic developmental process of the arcuate fasciculus (AF) using subcomponent diffusion tensor imaging (DTI) analysis in typically developing volunteers. DTI data were acquired from 96 consecutive typically developing children, aged 0–14 years. AF subcomponents, including the posterior, anterior, and direct AF tracts were analyzed. Success rates of analysis (AR) and fractional anisotropy (FA) values of each subcomponent tract were measured and compared. AR of all subcomponent tracts, except the posterior, showed a significant increase with aging (P < 0.05). Subcomponent tracts had a specific developmental sequence: First, the posterior AF tract, second, the anterior AF tract, and last, the direct AF tract in identical hemispheres. FA values of all subcomponent tracts, except right direct AF tract, showed correlation with subject’s age (P < 0.05). Increased AR and FA values were observed in female subjects in young age (0–2 years) group compared with males (P < 0.05). The direct AF tract showed leftward hemispheric asymmetry and this tendency showed greater consolidation in older age (3–14 years) groups (P < 0.05). These findings demonstrated the radiologic developmental patterns of the AF from infancy to adolescence using subcomponent DTI analysis. The AF showed a specific developmental sequence, sex difference in younger age, and hemispheric asymmetry in older age.

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    Rosiglitazone ameliorates diffuse axonal injury by reducing loss of tau and up-regulating caveolin-1 expression
    Yong-lin Zhao, Jin-ning Song, Xu-dong Ma, Bin-fei Zhang, Dan-dong Li, Hong-gang Pang
    2016, 11 (6):  944-950.  doi: 10.4103/1673-5374.184493
    Abstract ( 247 )   PDF (1411KB) ( 423 )   Save

    Rosiglitazone up-regulates caveolin-1 levels and has neuroprotective effects in both chronic and acute brain injury. Therefore, we postulated that rosiglitazone may ameliorate diffuse axonal injury via its ability to up-regulate caveolin-1, inhibit expression of amyloid-beta precursor protein, and reduce the loss and abnormal phosphorylation of tau. In the present study, intraperitoneal injection of rosiglitazone significantly reduced the levels of amyloid-beta precursor protein and hyperphosphorylated tau (phosphorylated at Ser404 (p-tau (S404)), and it increased the expression of total tau and caveolin-1 in the rat cortex. Our results show that rosiglitazone inhibits the expression of amyloid-beta precursor protein and lowers p-tau (S404) levels, and it reduces the loss of total tau, possibly by up-regulating caveolin-1. These actions of rosiglitazone may underlie its neuroprotective effects in the treatment of diffuse axonal injury.

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    Mechanisms responsible for the effect of median nerve electrical stimulation on traumatic brain injury-induced coma: orexin-A-mediated N-methyl-D-aspartate receptor subunit NR1 upregulation
    Zhen Feng, Qing Du
    2016, 11 (6):  951-956.  doi: 10.4103/1673-5374.184494
    Abstract ( 292 )   PDF (931KB) ( 513 )   Save

    Electrical stimulation of the median nerve is a noninvasive technique that facilitates awakening from coma. In rats with traumatic brain injury- induced coma, median nerve stimulation markedly enhances prefrontal cortex expression of orexin-A and its receptor, orexin receptor 1. To further understand the mechanism underlying wakefulness mediated by electrical stimulation of the median nerve, we evaluated its effects on the expression of the N-methyl-D-aspartate receptor subunit NR1 in the prefrontal cortex in rat models of traumatic brain injury-induced coma, using immunohistochemistry and western blot assays. In rats with traumatic brain injury, NR1 expression increased with time after injury. Rats that underwent electrical stimulation of the median nerve (30 Hz, 0.5 ms, 1.0 mA for 15 minutes) showed elevated NR1 expression and greater recovery of consciousness than those without stimulation. These effects were reduced by intracerebroventricular injection of the orexin receptor 1 antagonist SB334867. Our results indicate that electrical stimulation of the median nerve promotes recovery from traumatic brain injury-induced coma by increasing prefrontal cortex NR1 expression via an orexin-A-mediated pathway.

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    Large-conductance Ca2+-activated K+ channel involvement in suppression of cerebral ischemia/reperfusion injury after electroacupuncture at Shuigou (GV26) acupoint in rats
    Yong Wang, Yan Shen, Hai-ping Lin, Zhuo Li, Ying-ying Chen, Shu Wang
    2016, 11 (6):  957-962.  doi: 10.4103/1673-5374.184495
    Abstract ( 176 )   PDF (802KB) ( 604 )   Save

    Excess activation and expression of large-conductance Ca2+-activated K+ channels (BKCa channels) may be an important mechanism for delayed neuronal death after cerebral ischemia/reperfusion injury. Electroacupuncture can regulate BKCa channels after cerebral ischemia/ reperfusion injury, but the precise mechanism remains unclear. In this study, we established a rat model of cerebral ischemia/reperfusion injury. Model rats received electroacupuncture of 1 mA and 2 Hz at Shuigou (GV26) for 10 minutes, once every 12 hours for a total of six times in 72 hours. We found that in cerebral ischemia/reperfusion injury rats, ischemic changes in the cerebral cortex were mitigated after electroacupuncture. Moreover, BKCa channel protein and mRNA expression were reduced in the cerebral cortex and neurological function noticeably improved. These changes did not occur after electroacupuncture at a non-acupoint (5 mm lateral to the left side of Shuigou). Thus, our findings indicate that electroacupuncture at Shuigou improves neurological function in rats following cerebral ischemia/reperfusion injury, and may be associated with down-regulation of BKCa channel protein and mRNA expression. Additionally, our results suggest that the Shuigou acupoint has functional specificity.

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    Establishment of a rat model of chronic thoracolumbar cord compression with a flat plastic screw
    Yong Sun, Li-hai Zhang, Yang-mu Fu, Zhi-rui Li, Jian-heng Liu, Jiang Peng, Bin Liu, Pei-fu Tang
    2016, 11 (6):  963-970.  doi: 10.4103/1673-5374.184496
    Abstract ( 281 )   PDF (2178KB) ( 493 )   Save

    Previous studies of animal models of chronic mechanical compression of the spinal cord have mainly focused on cervical and thoracic lesions, but few studies have investigated thoracolumbar injury. The specific pathophysiological mechanism of chronic thoracolumbar cord injury has not yet been elucidated. The purpose of this study was to improve animal models of chronic thoracolumbar cord compression using the progressive screw. A custom-designed flat plastic screw was implanted in the spinal cord between thoracic vertebrae 12 and lumbar 1 of rats. The screw was tightened one complete turn (0.5 mm) every 7 days for 4 weeks to create different levels of chronic spinal cord compression. Following insertion of the screw, there was a significant decline in motor function of the hind limbs, and severe stenosis of micro-computed tomography parameters in the spinal cord. Cortical somatosensory evoked potential amplitudes were reduced remarkably, and latencies were prolonged at 30 minutes after surgery. The loss of motor neurons in the gray matter was marked. Demyelination and cavitation were observed in the white matter. An appropriate rat model of chronic thoracolumbar cord compression was successfully created using the progressive screw compression method, which simulated spinal cord compression injury.

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    Central neuromechanisms underlying control of intragastric pressure through acupuncture at Zusanli (ST36) in rats: the upper cervical cord is the key link between the ascending and descending pathways
    Chun-yan Yong, Shu Chen, Heng Chen, Xiao Chu, Chao Zhang, Cheng Tan, Lan Ye, Jiang-shan Li
    2016, 11 (6):  971-976.  doi: 10.4103/1673-5374.184497
    Abstract ( 305 )   PDF (1058KB) ( 697 )   Save

    Sensory inputs stimulated by Zusanli (ST36) acupuncture in the abdomen are known to converge in the upper cervical cord. However, it is unclear whether these inputs are subsequently conveyed to the hypothalamic paraventricular nucleus and what kind of afferent fibers are involved. We focused on the upper cervical cord, where afferent inputs converge, and detected c-fos expression in oxytocinergic neurons. We found that Zusanli acupuncture therapy effectively elevated intragastric pressure, but inhibited expression of c-fos in oxytocinergic neurons of the paraventricular nucleus in upper cervical cord injured rats. These Zusanli acupuncture effects remained even after complete dorsal cord transection. However, after complete transection of the spinal cord or dorsolateral funiculus, the effects were significantly attenuated and even disappeared. These findings suggest that the paraventricular nucleus is responsible for pooling and integrating signals from the Zusanli acupuncture and sensory information from the intragastric pressure variation, thereby contributing to the regulation of intragastric pressure. The upper cervical cord serves as the key link between ascending and descending pathways, which conveys afferent inputs to the paraventricular nucleus through the dorsolateral funiculus

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    Atorvastatin activates autophagy and promotes neurological function recovery after spinal cord injury
    Shuang Gao, Zhong-ming Zhang, Zhao-liang Shen, Kai Gao, Liang Chang, Yue Guo, Zhuo Li, Wei Wang, Ai-mei Wang
    2016, 11 (6):  977-982.  doi: http://orcid.org/0000-0002-6308-2870
    Abstract ( 335 )   PDF (764KB) ( 468 )   Save

    Atorvastatin, a lipid-lowering medication, provides neuroprotective effects, although the precise mechanisms of action remain unclear. Our previous studies confirmed activated autophagy following spinal cord injury, which was conducive to recovery of neurological functions. We hypothesized that atorvastatin could also activate autophagy after spinal cord injury, and subsequently improve recovery of neurological functions. A rat model of spinal cord injury was established based on the Allen method. Atorvastatin (5 mg/kg) was intraperitoneally injected at 1 and 2 days after spinal cord injury. At 7 days post-injury, western blot assay, reverse transcription-polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining results showed increased Beclin-1 and light chain 3B gene and protein expressions in the spinal cord injury + atorvastatin group. Additionally, caspase-9 and caspase-3 expression was decreased, and the number of TUNEL-positive cells was reduced. Compared with the spinal cord injury + saline group, Basso, Beattie, and Bresnahan locomotor rating scale scores significantly increased in the spinal cord injury + atorvastatin group at 14–42 days post-injury. These findings suggest that atorvastatin activated autophagy after spinal cord injury, inhibited apoptosis, and promoted recovery of neurological function.

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    ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro
    Xu-feng Jia, Fei Ye, Yan-bo Wang, Da-xiong Feng
    2016, 11 (6):  983-987.  doi: 10.4103/1673-5374.184499
    Abstract ( 434 )   PDF (813KB) ( 762 )   Save

    Spontaneous axonal regeneration of neurons does not occur after spinal cord injury because of inhibition by myelin and other inhibitory factors. Studies have demonstrated that blocking the Rho/Rho-kinase (ROCK) pathway can promote neurite outgrowth in spinal cord injury models. In the present study, we investigated neurite outgrowth and neuronal differentiation in neural stem cells from the mouse subventricular zone after inhibition of ROCK in vitro. Inhibition of ROCK with Y-27632 increased neurite length, enhanced neuronal differentiation, and upregulated the expression of two major signaling pathway effectors, phospho-Akt and phospho-mitogen-activated protein kinase, and the Hippo pathway effector YAP. These results suggest that inhibition of ROCK mediates neurite outgrowth in neural stem cells by activating the Hippo signaling pathway.

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    Indirubin-3′-monoxime suppresses amyloid-beta- induced apoptosis by inhibiting tau hyperphosphorylation
    Shu-gang Zhang, Xiao-shan Wang, Ying-dong Zhang, Qing Di, Jing-ping Shi, Min Qian, Li-gang Xu, Xing-jian Lin, Jie Lu
    2016, 11 (6):  988-993.  doi: 10.4103/1673-5374.184500
    Abstract ( 283 )   PDF (1078KB) ( 697 )   Save

    Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer’s disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SHSY5Y cells exposed to amyloid-beta 25–35 (Aβ25–35), and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β (GSK-3β). Our results suggest that indirubin- 3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer’s disease.

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    Transplantation of human adipose tissue-derived stem cells for repair of injured spiral ganglion neurons in deaf guinea pigs
    Sujeong Jang, Hyong-Ho Cho, Song-Hee Kim, Kyung-Hwa Lee, Yong-Bum Cho, Jong-Seong Park, Han-Seong Jeong
    2016, 11 (6):  994-1000.  doi: 10.4103/1673-5374.184503
    Abstract ( 256 )   PDF (1116KB) ( 711 )   Save

    Excessive noise, ototoxic drugs, infections, autoimmune diseases, and aging can cause loss of spiral ganglion neurons, leading to permanent sensorineural hearing loss in mammals. Stem cells have been confirmed to be able to differentiate into spiral ganglion neurons. Little has been reported on adipose tissue-derived stem cells (ADSCs) for repair of injured spiral ganglion neurons. In this study, we hypothesized that transplantation of neural induced-human ADSCs (NI-hADSCs) can repair the injured spiral ganglion neurons in guinea pigs with neomycin-induced sensorineural hearing loss. NI-hADSCs were induced with culture medium containing basic fibroblast growth factor and forskolin and then injected to the injured cochleae. Guinea pigs that received injection of Hanks’ balanced salt solution into the cochleae were used as controls. Hematoxylin-eosin staining showed that at 8 weeks after cell transplantation, the number of surviving spiral ganglion neurons in the cell transplantation group was significantly increased than that in the control group. Also at 8 weeks after cell transplantation, immunohistochemical staining showed that a greater number of NI-hADSCs in the spiral ganglions were detected in the cell transplantation group than in the control group, and these NI-hADSCs expressed neuronal markers neurofilament protein and microtubule-associated protein 2. Within 8 weeks after cell transplantation, the guinea pigs in the cell transplantation group had a gradually decreased auditory brainstem response threshold, while those in the control group had almost no response to 80 dB of clicks or pure tone burst. These findings suggest that a large amount of NI-hADSCs migrated to the spiral ganglions, survived for a period of time, repaired the injured spiral ganglion cells, and thereby contributed to the recovery of sensorineural hearing loss in guinea pigs.

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    miR-148b-3p promotes migration of Schwann cells by targeting cullin-associated and neddylation-dissociated 1
    Tian-mei Qian, Li-li Zhao, Jing Wang, Ping Li, Jing Qin, Yi-sheng Liu, Bin Yu, Fei Ding, Xiao-song Gu, Song-lin Zhou
    2016, 11 (6):  1001-1005.  doi: 10.4103/1673-5374.184504
    Abstract ( 289 )   PDF (1861KB) ( 481 )   Save

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively adjust gene expression in multifarious biological processes. However, the regulatory effects of miRNAs on Schwann cells remain poorly understood. Previous microarray analysis results have shown that miRNA expression is altered following sciatic nerve transaction, thereby affecting proliferation and migration of Schwann cells. This study investigated whether miR-148b-3p could regulate migration of Schwann cells by directly targeting cullin-associated and neddylation-dissociated 1 (Cand1). Up-regulated expression of miR-148b-3p promoted Schwann cell migration, whereas silencing of miR-148b-3p inhibited Schwann cell migration in vitro. Further experiments confirmed that Cand1 was a direct target of miR-148b-3p, and Cand1 knockdown reversed suppression of the miR-148b-3p inhibitor on Schwann cell migration. These results suggested that miR-148b-3p promoted migration of Schwann cells by directly targeting Cand1 in vitro.

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    Synergetic effects of ciliary neurotrophic factor and olfactory ensheathing cells on optic nerve reparation (complete translation)
    Dan-ping Yin, Qing-ying Chen, Lin Liu
    2016, 11 (6):  1006-1012.  doi: 10.4103/1673-5374.184505
    Abstract ( 298 )   PDF (1954KB) ( 676 )   Save

    At present, there is no effective treatment for the repair of the optic nerve after injury, or improvement of its microenvironment for regeneration. Intravitreally injected ciliary neurotrophic factor (CNTF) and olfactory ensheathing cells (OECs) promote the long-distance regrowth of severed optic nerve fibers after intracranial injury. Here, we examined the efficacy of these techniques alone and in combination, in a rat model of optic nerve injury. We injected condensed OEC suspension at the site of injury, or CNTF into the vitreous body, or both simultaneously. Retrograde tracing techniques showed that 4 weeks postoperatively, the number of surviving retinal ganglion cells and their axonal density in the optic nerve were greater in rats subjected to OEC injection only than in those receiving CNTF injection only. Furthermore, combined OEC + CNTF injection achieved better results than either monotherapy. These findings confirm that OECs are better than CNTF at protecting injured neurons in the eye, but that combined OEC and CNTF therapy is notably more effective than either treatment alone.

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    Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies
    Guihong Li, Fengbo Yu, Ting Lei, Haijun Gao, Peiwen Li, Yuxue Sun, Haiyan Huang, Qingchun Mu
    2016, 11 (6):  1015-1024.  doi: 10.4103/1673-5374.184506
    Abstract ( 214 )   PDF (590KB) ( 663 )   Save

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research.

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