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    25 July 2014, Volume 9 Issue 14 Previous Issue    Next Issue
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    Bridging long gap peripheral nerve injury using skeletal muscle-derived multipotent stem cells
    Tetsuro Tamaki
    2014, 9 (14):  1333-1336.  doi: 10.4103/1673-5374.137582
    Abstract ( 240 )   PDF (1789KB) ( 1004 )   Save

    Long gap peripheral nerve injuries usually reulting in life-changing problems for patients. Skeletal muscle derived-multipotent stem cells (Sk-MSCs) can differentiate into Schwann and perineurial/endoneurial cells, vascular relating pericytes, and endothelial and smooth muscle cells in the damaged peripheral nerve niche. Application of the Sk-MSCs in the bridging conduit for repairing long nerve gap injury resulted favorable axonal regeneration, which showing superior effects than gold standard therapy--healthy nerve autograft. This means that it does not need to sacrifice of healthy nerves or loss of related functions for repairing peripheral nerve injury.

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    Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury
    Peter D. Drummond
    2014, 9 (14):  1337-1340. 
    Abstract ( 235 )   PDF (183KB) ( 764 )   Save

    Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the production and release of pro-inflammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alpha1A-adrenoceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alpha1-adrenoceptors to increase the production of the pro-inflammatory cytokine interleukin-6. In addition, the release of inflammatory mediators and nerve growth factor from keratinocytes and other cells may augment the expression of alpha1-adrenoceptors on peripheral nerve fibers. Consequently, nociceptive afferents acquire an abnormal excitability to adrenergic agents, and inflammatory processes build. These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome.

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    Adipose derived stem cells and nerve  regeneration
    Alessandro Faroni, Richard JP Smith, Adam J Reid
    2014, 9 (14):  1341-1346.  doi: 10.4103/1673-5374.137585
    Abstract ( 252 )   PDF (205KB) ( 1133 )   Save

    Injuries to peripheral nerves are common and cause life-changing problems for patients alongside high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacrificing a section of nerve from elsewhere in the body to provide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacrifice of a functional nerve. Stem cells are prime candidates as accelerators of regeneration in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

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    Strategies for myelin regeneration: lessons learned from development
    Abhay Bhatt, Lir-Wan Fan, Yi Pang
    2014, 9 (14):  1347-1350.  doi: 10.4103/1673-5374.137586
    Abstract ( 259 )   PDF (188KB) ( 889 )   Save

    Myelin regeneration is indispensably important for patients suffering from several central nervous system (CNS) disorders such as multiple sclerosis (MS) and spinal cord injury (SCI), because it is not only essential for restoring neurophysiology, but also protects denuded axons for secondary degeneration. Understanding the cellular and molecular mechanisms underlying remyelination is critical for the development of remyelination-specific therapeutic approaches. As remyelination shares certain common mechanisms with developmental myelination, knowledge from study of developmental myelination contributes greatly to emerging myelin regeneration therapies, best evidenced as the recently developed human anti-Nogo receptor interacting protein-1 (LINGO-1) monoclonal antibodies to treat MS patients in clinical trials.

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    An inside-out vein graft filled with platelet-rich plasma for repair of a short sciatic nerve defect in rats
    Ji Yeong Kim, Woo Joo Jeon, Dong Hwee Kim, Im Joo Rhyu, Young Hwan Kim, Inchan Youn, Jong Woong Park
    2014, 9 (14):  1351-1357.  doi: 10.4103/1673-5374.137587
    Abstract ( 227 )   PDF (1356KB) ( 788 )   Save

    Platelet-rich plasma containing various growth factors can promote nerve regeneration. An inside-out vein graft can substitute nerve autograft to repair short nerve defects. It is hypothesized that an inside-out vein graft filled with platelet-rich plasma shows better effects in the repair of short sciatic nerve defects. In this study, an inside-out vein autograft filled with platelet-rich plasma was used to bridge a 10 mm-long sciatic nerve defect in rats. The sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better improved than that of rats with a simple inside-out vein autograft. At 6 and 8 weeks, the sciatic nerve function of rats with an inside-out vein autograft filled with platelet-rich plasma was better than that of rats undergoing nerve autografting. Compared with the sciatic nerve repaired with a simple inside-out vein autograft, the number of myelinated axons was higher, axon diameter and myelin sheath were greater in the sciatic nerve repaired with an inside-out vein autograft filled with platelet-rich plasma and they were similar to those in the sciatic nerve repaired with nerve autograft. These findings suggest that an inside-out vein graft filled with platelet-rich plasma can substitute nerve autograft to repair short sciatic nerve defects.

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    Chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor promotes sciatic nerve repair
    Yanru Zhang, Hui Zhang, Kaka Katiella, Wenhua Huang
    2014, 9 (14):  1358-1364.  doi: 10.4103/1673-5374.137588
    Abstract ( 139 )   PDF (480KB) ( 780 )   Save

    A chemically extracted acellular allogeneic nerve graft can reduce postoperative immune rejection, similar to an autologous nerve graft, and can guide neural regeneration. However, it remains poorly understood whether a chemically extracted acellular allogeneic nerve graft combined with neurotrophic factors provides a good local environment for neural regeneration. This study investigated the repair of injured rat sciatic nerve using a chemically extracted acellular allogeneic nerve graft combined with ciliary neurotrophic factor. An autologous nerve anastomosis group and a chemical acellular allogeneic nerve bridging group were prepared as controls. At 8 weeks after repair, sciatic functional index, evoked potential amplitude of the soleus muscle, triceps wet weight recovery rate, total number of myelinated nerve fibers and myelin sheath thickness were measured. For these indices, values in the three groups showed the autologous nerve anastomosis group > chemically extracted acellular nerve graft + ciliary neurotrophic factor group > chemical acellular allogeneic nerve bridging group. These results suggest that chemically extracted acellular nerve grafts combined with ciliary neurotrophic factor can repair sciatic nerve defects, and that this repair is inferior to autologous nerve anastomosis, but superior to chemically extracted acellular allogeneic nerve bridging alone.

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    Electroacupuncture attenuates neuropathic pain after brachial plexus injury
    Shenyu Zhang, Hailiang Tang, Junming Zhou, Yudong Gu
    2014, 9 (14):  1365-1370.  doi: 10.4103/1673-5374.137589
    Abstract ( 330 )   PDF (1078KB) ( 1313 )   Save

    Electroacupuncture has traditionally been used to treat pain, but its effect on pain following brachial plexus injury is still unknown. In this study, rat models of an avulsion injury to the left brachial plexus root (associated with upper-limb chronic neuropathic pain) were given electroacupuncture stimulation at bilateral Quchi (LI11), Hegu (LI04), Zusanli (ST36) and Yanglingquan (GB34). After electroacupuncture therapy, chronic neuropathic pain in the rats’ upper limbs was significantly attenuated. Immunofluorescence staining showed that the expression of β-endorphins in the arcuate nucleus was significantly increased after therapy. Thus, experimental findings indicate that electroacupuncture can attenuate neuropathic pain after brachial plexus injury through upregulating β-endorphin expression.

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    Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve
    Lanfeng Huang, Rui Li, Wanguo Liu, Jin Dai, Zhenwu Du, Xiaonan Wang, Jianchao Ma, Jinsong Zhao
    2014, 9 (14):  1371-1378.  doi: 10.4103/1673-5374.137590
    Abstract ( 159 )   PDF (3592KB) ( 816 )   Save

    Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

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    Green tea polyphenols protect spinal cord neurons against hydrogen peroxide-induced oxidative stress
    Jianbo Zhao, Zhengkai Zhao, Shiqiang Fang, Yajiang Yuan, Zhanpeng Guo, Jinhao Zeng, Yue Guo, Peifu Tang, Xifan Mei
    2014, 9 (14):  1379-1385.  doi: 10.4103/1673-5374.137591
    Abstract ( 232 )   PDF (620KB) ( 1409 )   Save

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    Ultrasound imaging of chitosan nerve conduits that bridge sciatic nerve defects in rats
    Xiaoyang Chen, Yifei Yin, Tingting Zhang, Yahong Zhao, Yumin Yang, Xiaomei Yu, Hongkui Wang
    2014, 9 (14):  1386-1388.  doi: 10.4103/1673-5374.137592
    Abstract ( 243 )   PDF (1037KB) ( 934 )   Save

    The repair of peripheral nerve injuries with autologous nerve remains the gold standard (Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014). With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury (Wang et al., 2012; Sví?enská et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; Moya-Díaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014). Therefore, new simple and effective methods are needed to better evaluate the outcomes of repair using nerve conduits in vivo. Ultrasound is a common noninvasive clinical detection modality that has been used in many fields. However, ultrasound has only rarely been used to observe implanted nerve conduits in vivo. Haug et al. (2013) tried to displace the collagen nerve conduit for repairing the digital nerve under ultrasound. Here, we report the first use of ultrasound to noninvasively observe the changes in chitosan nerve conduits implanted in rats over time.

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    Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases
    Yunqian Zhang, Jintao Li, Tingjuan Wang, Jianlin Wang
    2014, 9 (14):  1389-1394.  doi: 10.4103/1673-5374.137593
    Abstract ( 237 )   PDF (328KB) ( 1174 )   Save

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

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    Heat shock protein 72 confers protection in  retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model
    Ning Li, Yuehua Li, Xuanchu Duan
    2014, 9 (14):  1395-1401.  doi: 10.4103/1673-5374.137595
    Abstract ( 233 )   PDF (773KB) ( 1003 )   Save

    Optic nerve transection increased the expression of heat shock protein 72 (HSP72) in the lateral geniculate body, indicating that this protein is involved in the prevention of neuronal injury. Zinc sulfate and quercetin induced and inhibited the expression of HSP72, respectively. Intraperitoneal injections of zinc sulfate, SP600125 (c-Jun N-terminal kinase inhibitor), or quercetin were performed on retinal ganglion cells in a Wistar rat model of chronic ocular hypertension. Our results showed that compared with the control group, the expression of HSP72 in retinal ganglion cells and the lateral geniculate body was increased after the injection of zinc sulfate, but was decreased after the injection of quercetin. The expression of phosphorylated c-Jun N-terminal kinases and phosphorylated c-Jun were visible 3 days after injection in the control group, and reached a peak at 7 days. Zinc sulfate and SP600125 significantly decreased the expression of p-c-Jun, whereas quercetin significantly enhanced the expression of this protein. These results suggest that HSP72 protects retinal ganglion cells and lateral geniculate body in a rat model of chronic ocular hypertension from injury by blocking the activation of the stress-activated kinase/c-Jun N-terminal kinase apoptotic pathway.

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    Cholecystokinin octapeptide antagonizes apoptosis in human retinal pigment epithelial cells
    Yuan Liu, Yueling Zhang, Zhaohui Gu, Lina Hao, Juan Du, Qian Yang, Suping Li, Liying Wang, Shilei Gong
    2014, 9 (14):  1402-1408.  doi: 10.4103/1673-5374.137596
    Abstract ( 339 )   PDF (422KB) ( 856 )   Save

    Although cholecystokinin octapeptide-8 is important for neurological function, its neuroprotective properties remain unclear. We speculated that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against oxidative injury. In this study, retinal pigment epithelial cells were treated with peroxynitrite to induce oxidative stress. Peroxynitrite triggered apoptosis in these cells, and increased the expression of Fas-associated death domain, Bax, caspa-
    se-8 and Bcl-2. These changes were suppressed by treatment with cholecystokinin octapeptide-8. These results suggest that cholecystokinin octapeptide-8 can protect human retinal pigment epithelial cells against apoptosis induced by peroxynitrite.

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