Table of Content

15 January 2018, Volume 13 Issue 1 Previous Issue    Next Issue

For Selected:

Download Citations EndNote Reference Manager ProCite BibTeX RefWorks

Toggle Thumbnails

Select

LETTER FROM THE EDITORS-IN-CHIEF Kwok-fai So, Xiao-Ming Xu 2018, 13 (1):  5-6.  Abstract ( 156 )   PDF (730KB) ( 502 )   Save Related Articles | Metrics

Select

Brain injury and neural stem cells Parker E. Ludwig, Finosh G. Thankam, Arun A. Patil, Andrea J. Chamczuk, Devendra K. Agrawal 2018, 13 (1):  7-18.  doi: doi: 10.4103/1673-5374.224361 Abstract ( 212 )   PDF (832KB) ( 424 )   Save Many therapies with potential for treatment of brain injury have been investigated. Few types of cells have spurred as much interest and excitement as stem cells over the past few decades. The multipotentiality and self-renewing characteristics of stem cells confer upon them the capability to regenerate lost tissue in ischemic or degenerative conditions as well as trauma. While stem cells have not yet proven to be clinically effective in many such conditions as was once hoped, they have demonstrated some effects that could be manipulated for clinical benefit. The various types of stem cells have similar characteristics, and largely differ in terms of origin; those that have differentiated to some extent may exhibit limited capability in differentiation potential. Stem cells can aid in decreasing lesion size and improving function following brain injury. Related Articles | Metrics

Select

Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer’s disease Isaac G. Onyango 2018, 13 (1):  19-25.  doi: 10.4103/1673-5374.224362 Abstract ( 189 )   PDF (357KB) ( 405 )   Save   Alzheimer’s disease (AD) is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria. Related Articles | Metrics

Select

Tackling dipeptidyl peptidase IV in neurological disorders Ghaith Al-Badri, Gian Marco Leggio, Giuseppe Musumeci, Rubina Marzagalli, Filippo Drago, Alessandro Castorina 2018, 13 (1):  26-34.  doi: 10.4103/1673-5374.224365 Abstract ( 205 )   PDF (323KB) ( 301 )   Save Dipeptidyl peptidase IV (DPP-IV) is a serine protease best known for its role in inactivating glucagon-like peptide-1 (GLP-1), pituitary adenylate cyclase-activating polypeptide (PACAP) and glucose-dependent insulinotropic peptide (GIP), three stimulators of pancreatic insulin secretion with beneficial effects on glucose disposal. Owing to the relationship between DPP-IV and these peptides, inhibition of DPP-IV enzyme activity is considered as an attractive treatment option for diabetic patients. Nonetheless, increasing studies support the idea that DPP-IV might also be involved in the development of neurological disorders with a neuroinflammatory component, potentially through its non-incretin activities on immune cells. In this review article, we aim at highlighting recent literature describing the therapeutic value of DPP-IV inhibitors for the treatment of such neurological conditions. Finally, we will illustrate some of the promising results obtained using berberine, a plant extract with potent inhibitory activity on DPP-IV. Related Articles | Metrics

Select

Stem cells for spinal cord injuries bearing translational potential Kyriakos Dalamagkas, Magdalini Tsintou, Alexander M. Seifalian 2018, 13 (1):  35-42.  doi: 10.4103/1673-5374.224360 Abstract ( 184 )   PDF (662KB) ( 381 )   Save  Spinal cord injury (SCI) is a highly debilitating neurological disease, which still lacks effective treatment strategies, causing significant financial burden and distress to the affected families. Nevertheless, nanotechnology and regenerative medicine strategies holding promise for the development of novel therapies that would reach from bench to bedside to serve the SCI patients. There has already been significant progress in the field of cell-based therapies, with the clinical application for SCI, currently in phase II of the clinical trial. Stem cells (e.g., induced pluripotent stem cells, fetal stem cells, human embryonic stem cells, and olfactory ensheathing cells) are certainly not to be considered the panacea for neural repair but, especially when combined with rehabilitation or other combinatorial approaches using the help of nanotechnology, they seem to be the source of some of the most promising and clinical translatable cell-based therapies that could help solving impactful problems on neural repair. Related Articles | Metrics

Select

A growing feld: the regulation of axonal regeneration by Wnt signaling Armando L. Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S. Hackam 2018, 13 (1):  43-52.  doi: 10.4103/1673-5374.224359 Abstract ( 211 )   PDF (870KB) ( 490 )   Save The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury. Related Articles | Metrics

Select

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery afer peripheral nerve injuries George D. Bittner, Dale R. Sengelaub, Cameron L. Ghergherehchi 2018, 13 (1):  53-57.  doi: 10.4103/1673-5374.224363 Abstract ( 159 )   PDF (945KB) ( 370 )   Save Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory signaling, and motor control; (2) Wallerian rapid (1-3 days) degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months (if ever, after ablations) by slowly-regenerating (1 mm/d), proximal-stump outgrowths that must specifically reinnervate denervated targets; (3) Poor acceptance of microsutured nerve allografts, even if tissue-matched and immune-suppressed. Repair of transections/ablations by neurorrhaphy and well-specified-sequences of PEG-fusion solutions (one containing polyethylene glycol, PEG) successfully address these problems. However, conundrums and confusions regarding unorthodox and dramatic results of PEG-fusion repair in animal model systems often lead to misunderstandings. For example, (1) Axonal continuity and signaling is re-established within minutes by non-specifically PEG-fusing (connecting) severed motor and sensory axons across each lesion site, but remarkable behavioral recovery to near-unoperated levels takes several weeks; (2) Many distal stumps of inappropriately-reconnected, PEG-fused axons do not ever (Wallerian) degenerate and continuously innervate muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (3) Host rats do not reject PEG-fused donor nerve allografts in a non-immuno-privileged environment with no tissue matching or immunosuppression; (4) PEG fuses apposed open axonal ends or seals each shut (thereby preventing PEG-fusion), depending on the experimental protocol; (5) PEG-fusion protocols produce similar results in animal model systems and early human case studies. Hence, iconoclastic PEG-fusion data appropriately understood might provoke a re-thinking of some Neuroscience dogma and a paradigm shift in clinical treatment of peripheral nerve injuries. Related Articles | Metrics

Select

Optical read-out and modulation of peripheral nerve activity Arjun K. Fontaine, Hans E. Anderson, John H. Caldwell, Richard F. Weir 2018, 13 (1):  58-61.  doi: 10.4103/1673-5374.224364 Abstract ( 169 )   PDF (293KB) ( 279 )   Save Numerous clinical and research applications necessitate the ability to interface with peripheral nerve fibers to read and control relevant neural pathways. Visceral organ modulation and rehabilitative prosthesis are two areas which could benefit greatly from improved neural interfacing approaches. Therapeutic neural interfacing, or ‘bioelectronic medicine’, has potential to affect a broad range of disorders given that all the major organs of the viscera are neurally innervated. However, a better understanding of the neural pathways that underlie function and a means to precisely interface with these fibers are required. Existing peripheral nerve interfaces, consisting primarily of electrode-based designs, are unsuited for highly specific (individual axon) communication and/or are invasive to the tissue. Our laboratory has explored an optogenetic approach by which optically sensitive reporters and actuators are targeted to specific cell (axon) types. The nature of such an approach is laid out in this short perspective, along with associated technologies and challenges. Related Articles | Metrics

Select

Screening antioxidants for the protection of cochlear sensory cells Dong Gu Hur, Arwa Kurabi, Allen F. Ryan 2018, 13 (1):  62-64.  doi: 10.4103/1673-5374.224371 Abstract ( 139 )   PDF (459KB) ( 417 )   Save Sensory cell damage is a major cause of hearing loss: Sensorineural hearing loss (SNHL) is a common sensory deficit characterized by tissue damage and/or cell death in the cochlea.Moderate and severe SNHL causes deficits in communication,associated with increased isolation from human relationships,and negativly impacts employability. Many etiologies have been associated with SNHL: Noise overexposure, certain drugs, inner or middle ear infection or immune-induced inflammation being common. However, the most prevalent form of SNHL is presbycusis or age-related hearing loss, often aggravated by other factors including a history of noise exposure, diabetes or high blood pressure (Wong and Ryan, 2015). Though systemic steroids are used in the treatment of sudden SNHL, other drugs to prevent or cure hearing loss have not yet been developed.Cochlear sensory cells, known as hair cells (HCs) and neurons have very limited repair capacity. Moreover since these cells do not regenerate, making any loss permanent, prevention of cell damage is critical to protecting hearing. Related Articles | Metrics

Select

Diabetes, its impact on peripheral nerve regeneration: lessons from pre-clinical rat models towards nerve repair and reconstruction Kirsten Haastert-Talini, Lars B. Dahlin 2018, 13 (1):  65-66.  doi: 10.4103/1673-5374.224370 Abstract ( 159 )   PDF (125KB) ( 374 )   Save The global number of patients with type 1 and type 2 diabetes is about to increase substantially in the coming decades. The reasons for this are two-fold, at first there is actual increase in incidence of type 1 diabetes and at second there is global increase in living expectancy and a high prevalence of patients with type 2 diabetes among the elderly. The diabetic condition is affiliated with reduced peripheral nervous system maintenance, such as peripheral neuropathies (Juster-Switlyk and Smith, 2016) that may be more common in men. Related Articles | Metrics

Select

Astrocytes in the cerebral cortex play a role in the spontaneous motor recovery following experimental striatal hemorrhage Juliana Dalibor Neves, Régis Gemerasca Mestriner, Carlos Alexandre Netto 2018, 13 (1):  67-68.  doi: 10.4103/1673-5374.224372 Abstract ( 126 )   PDF (119KB) ( 285 )   Save Intracerebral hemorrhage (ICH) is a stroke subtype caused by spontaneous rupture of small vessels and bleeding into the brain parenchyma,resulting in cell death and sensorimotor deficits. Despite the greater prevalence of the ischemic form of stroke (87%), ICH has the highest mortality rate of all stroke subtypes. The striatum is the most affected structure in hemorrhagic stroke (35–70%), followed by cerebral cortex (15–30%), brain stem and cerebellum (5–10%); patients suffering striatal and/or cortical ICH bear persistent sensorimotor disabilities. Although chronic sensorimotor impairment is established,a considerable amount of patients experience some degree of spontaneous recovery during the first six months after stroke (Qureshi et al., 2009), and the neurobiological basis of this process is not understood. Related Articles | Metrics

Select

Predictors of short-term outcome in patients with acute middle cerebral artery occlusion: unsuitability of ?uid-attenuated inversion recovery vascular hyperintensity scores Chan-chan Li, Xiao-zhu Hao, Jia-qi Tian, Zhen-wei Yao, Xiao-yuan Feng, Yan-mei Yang 2018, 13 (1):  69-76.  doi: 10.4103/1673-5374.224375 Abstract ( 147 )   PDF (549KB) ( 394 )   Save Fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) is used to assess leptomeningeal collateral circulation, but clinical outcomes of patients with FVH can be very different. The aim of the present study was to assess a FVH score and explore its relationship with clinical outcomes. Patients with acute ischemic stroke due to middle cerebral artery M1 occlusion underwent magnetic resonance imaging and were followed up at 10 days (National Institutes of Health Stroke Scale) and 90 days (modified Rankin Scale) to determine short-term clinical outcomes. Effective collateral circulation indirectly improved recovery of neurological function and short-term clinical outcome by extending the size of the pial penumbra and reducing infarct lesions. FVH score showed no correlation with 90-day functional clinical outcome and was not sufficient as an independent predictor of short-term clinical outcome. Related Articles | Metrics

Select

Intravenous morphine self-administration alters accumbal microRNA profiles in the mouse brain Juhwan Kim, Heh-In Im, Changjong Moon 2018, 13 (1):  77-85.  doi: 10.4103/1673-5374.224374 Abstract ( 196 )   PDF (1714KB) ( 377 )   Save A significant amount of evidence indicates that microRNAs (miRNAs) play an important role in drug addiction. The nucleus accumbens (NAc) is a critical part of the brain’s reward circuit and is involved in a variety of psychiatric disorders, including depression, anxiety, and drug addiction. However, few studies have examined the expression of miRNAs and their functional roles in the NAc under conditions of morphine addiction. In this study, mice were intravenously infused with morphine (0.01, 0.03, 0.3, 1 and 3 mg/kg/infusion) and showed inverted U-shaped response. After morphine self-administration, NAc was used to analyze the functional networks of altered miRNAs and their putative target mRNAs in the NAc following intravenous self-administration of morphine. We utilized several bioinformatics tools, including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping and CyTargetLinker. We found that 62 miRNAs were altered and exhibited differential expression patterns. The putative targets were related to diverse regulatory functions, such as neurogenesis, neurodegeneration, and synaptic plasticity, as well as the pharmacological effects of morphine (receptor internalization/endocytosis). The present findings provide novel insights into the regulatory mechanisms of accumbal molecules under conditions of morphine addiction and identify several novel biomarkers associated with morphine addiction. Related Articles | Metrics

Select

Electroacupuncture preconditioning protects against focal cerebral ischemia/reperfusion injury via suppression of dynamin-related protein 1 Gao-feng Zhang, Pei Yang, Zeng Yin, Huai-long Chen, Fu-guo Ma, Bin Wang, Li-xin Sun, Yan-lin Bi, Fei Shi, Ming-shan Wang 2018, 13 (1):  86-93.  doi: 10.4103/1673-5374.224373 Abstract ( 144 )   PDF (1569KB) ( 500 )   Save Electroacupuncture preconditioning at acupoint Baihui (GV20) can reduce focal cerebral ischemia/reperfusion injury. However, the precise protective mechanism remains unknown. Mitochondrial fission mediated by dynamin-related protein 1 (Drp1) can trigger neuronal apoptosis following cerebral ischemia/reperfusion injury. Herein, we examined the hypothesis that electroacupuncture pretreatment can regulate Drp1, and thus inhibit mitochondrial fission to provide cerebral protection. Rat models of focal cerebral ischemia/reperfusion injury were established by middle cerebral artery occlusion at 24 hours after 5 consecutive days of preconditioning with electroacupuncture at GV20 (depth 2 mm, intensity 1 mA, frequency 2/15 Hz, for 30 minutes, once a day). Neurological function was assessed using the Longa neurological deficit score. Pathological changes in the ischemic penumbra on the injury side were assessed by hematoxylin-eosin staining. Cellular apoptosis in the ischemic penumbra on the injury side was assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling staining. Mitochondrial ultrastructure in the ischemic penumbra on the injury side was assessed by transmission electron microscopy. Drp1 and cytochrome c expression in the ischemic penumbra on the injury side were assessed by western blot assay. Results showed that electroacupuncture preconditioning decreased expression of total and mitochondrial Drp1, decreased expression of total and cytosolic cytochrome c, maintained mitochondrial morphology and reduced the proportion of apoptotic cells in the ischemic penumbra on the injury side, with associated improvements in neurological function. These data suggest that electroacupuncture preconditioning-induced neuronal protection involves inhibition of the expression and translocation of Drp1. Related Articles | Metrics

Select

Is it necessary to use the entire root as a donor when transferring contralateral C7 nerve to repair median nerve? Kai-ming Gao, Jie Lao, Wen-jie Guan, Jing-jing Hu 2018, 13 (1):  94-99.  doi: 10.4103/1673-5374.224376 Abstract ( 140 )   PDF (747KB) ( 326 )   Save If a partial contralateral C7 nerve is transferred to a recipient injured nerve, results are not satisfactory. However, if an entire contralateral C7  nerve is used to repair two nerves, both recipient nerves show good recovery. These findings seem contradictory, as the above two methods use the same donor nerve, only the cutting method of the contralateral C7  nerve is different. To verify whether this can actually result in different repair effects, we divided rats with right total brachial plexus injury into three groups. In the entire root group, the entire contralateral C7  root was transected and transferred to the median nerve of the affected limb. In the posterior division group, only the posterior division of the contralateral C7  root was transected and transferred to the median nerve. In the entire root + posterior division group, the entire contralateral C7  root was transected but only the posterior division was transferred to the median nerve. After neurectomy,the median nerve was repaired on the affected side in the three groups. At 8, 12, and 16 weeks postoperatively, electrophysiological examination showed that maximum amplitude, latency, muscle tetanic contraction force, and muscle fiber cross-sectional area of the flexor digitorum superficialis muscle were significantly better in the entire root and entire root + posterior division groups than in the posterior division group. No significant difference was found between the entire root and entire root + posterior division groups. Counts of myelinated axons in the median nerve were greater in the entire root group than in the entire root + posterior division group, which were greater than the posterior division group. We conclude that for the same recipient nerve, harvesting of the entire contralateral C7  root achieved significantly better recovery than partial harvesting, even if only part of the entire root was used for transfer. This result indicates that the entire root should be used as a donor when transferring contralateral C7  nerve. Related Articles | Metrics

Select

Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration. Marcela Fernandes, Sandra Gomes Valente, Rodrigo Guerra Sabongi, João Baptista Gomes dos Santos, Vilnei Mattioli Leite,Henning Ulrich, Arthur Andrade Nery, Maria José da Silva Fernandes 2018, 13 (1):  100-104.  doi: 10.4103/1673-5374.224378 Abstract ( 175 )   PDF (828KB) ( 362 )   Save Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs) can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs (BMSCs) is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs (ADSCs) have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups: sham (only sciatic nerve exposed), Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle), ADSCs (sciatic nerve injury + intravenous MG containing ADSCs), and BMSCs (sciatic nerve injury + intravenous MG containing BMSCs) groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury,increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal diameter/fiber diameter ratios) in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for engraftment. Related Articles | Metrics

Select

Optimization of micropatterned poly(lactic-coglycolic acid) films for enhancing dorsal root ganglion cell orientation and extension Ching-Wen Li, Brett Davis, Jill Shea, Himanshu Sant, Bruce Kent Gale, Jayant Agarwal 2018, 13 (1):  105-111.  doi: 10.4103/1673-5374.224377 Abstract ( 183 )   PDF (1849KB) ( 359 )   Save Nerve conduits have been a viable alternative to the ‘gold standard’ autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion (DRG) cells on poly(lactic-co-glycolic acid) (PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation.Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1 (ridge/groove width parameters are equal, i.e., 10 μm/10 μm (even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1 (groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1 (ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices. Related Articles | Metrics

Select

Effect of moxibustion on mTOR-mediated autophagy in rotenone-induced Parkinson’s disease model rats Shu-ju Wang, Qi Wang, Jun Ma, Pei-hao Yu, Zhong-ming Wang, Bin Wang 2018, 13 (1):  112-118.  doi: 10.4103/1673-5374.224380 Abstract ( 161 )   PDF (484KB) ( 344 )   Save Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson’s disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson’s disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4)and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days. Model rats without any treatment were used as a sham control. Compared with the Parkinson’s disease group, the moxibustion group showed significantly greater tyrosine hydroxylase immunoreactivity and expression of light chain 3-II protein in the substantia nigra, and their behavioral score, α-synuclein immunoreactivity,the expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase (p-p70S6K) in the substantia nigra were significantly lower. These results suggest that moxibustion can promote the autophagic clearance of α-syn and improve behavioral performance in Parkinson’s disease model rats. The protective mechanism may be associated with suppression of the mTOR/p70S6K pathway. Related Articles | Metrics

Select

Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury? Jiri Ruzicka, Lucia Machova Urdzikova, Barbora Svobodova, Anubhav G. Amin3, Kristyna Karova, Jana Dubisova, Kristyna Zaviskova,Sarka Kubinova, Meic Schmidt, Meena Jhanwar-Uniyal, Pavla Jendelova, 2018, 13 (1):  119-127.  doi: 10.4103/1673-5374.224379 Abstract ( 201 )   PDF (1082KB) ( 346 )   Save Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin,60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and mmunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2,interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident. Related Articles | Metrics

Select

Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway. Hong-liang Song, Xiang Zhang, Wen-zhao Wang, Rong-han Liu, Kai Zhao, Ming-yuan Liu, Wei-ming Gong, Bin Ning 2018, 13 (1):  128-134.  doi: 10.4103/1673-5374.217349 Abstract ( 281 )   PDF (485KB) ( 426 )   Save Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase (p38 MAPK) pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin (30 mg/kg) for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway. Related Articles | Metrics

Select

PTEN knockdown with the Y444F mutant AAV2 vector promotes axonal regeneration in the adult optic nerve Zheng-ru Huang, Hai-ying Chen, Zi-zhong Hu, Ping Xie, Qing-huai Liu 2018, 13 (1):  135-144.  doi: 10.4103/1673-5374.224381 Abstract ( 192 )   PDF (2145KB) ( 388 )   Save The lack of axonal regeneration is the major cause of vision loss after optic nerve injury in adult mammals. Activating the PI3K/AKT/mTOR signaling pathway has been shown to enhance the intrinsic growth capacity of neurons and to facilitate axonal regeneration in the central nervous system after injury. The deletion of the mTOR negative regulator phosphatase and tensin homolog (PTEN) enhances regeneration of adult corticospinal neurons and ganglion cells. In the present study, we used a tyrosine-mutated (Y444F) AAV2 vector to efficiently express a short hairpin RNA (shRNA) for silencing PTEN expression in retinal ganglion cells. We evaluated cell survival and axonal regeneration in a rat model of optic nerve axotomy. The rats received an intravitreal injection of wildtype AAV2 or Y444F mutant AAV2 (both carrying shRNA to PTEN) 4 weeks before optic nerve axotomy. Compared with the wildtype AAV2 vector, the Y444F mutant AAV2 vector enhanced retinal ganglia cell survival and stimulated axonal regeneration to a greater extent 6 weeks after axotomy. Moreover,post-axotomy injection of the Y444F AAV2 vector expressing the shRNA to PTEN rescued ~19% of retinal ganglion cells and induced axons to regenerate near to the optic chiasm. Taken together, our results demonstrate that PTEN knockdown with the Y444F AAV2 vector promotes retinal ganglion cell survival and stimulates long-distance axonal regeneration after optic nerve axotomy. Therefore, the Y444F AAV2 vector might be a promising gene therapy tool for treating optic nerve injury. Related Articles | Metrics

Select

Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve NaRi Seo, Sung-Ho Lee, Kyung Won Ju, JaeMan Woo, BongJu Kim, SoungMin Kim, Jeong Won Jahng, Jong-Ho Lee 2018, 13 (1):  145-153.  doi: 10.4103/1673-5374.224383 Abstract ( 177 )   PDF (1678KB) ( 320 )   Save Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments.In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 106 cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and more DiI-labeled neurons in the trigeminal ganglia, contributing to rapider functional recovery of injured mental nerve. These findings suggest that low-frequency PEMF pretreatment is a promising approach to enhance the efficacy of cell therapy for peripheral nerve injury repair. Related Articles | Metrics

Select

Critical role of SDF-1/CXCR4 signaling pathway in stem cell homing in the deafened rat cochlea after acoustic trauma Ali Asghar Peyvandi, Navid Ahmady Roozbahany, Hassan Peyvandi, Hojjat-Allah Abbaszadeh, Niloofar Majdinasab,Mohammad Faridan, Somayeh Niknazar 2018, 13 (1):  154-160.  doi: 10.4103/1673-5374.224382 Abstract ( 158 )   PDF (1192KB) ( 495 )   Save Previous animal studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling pathway plays an important role in the targeted migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the injured area. In the present study, we aimed to investigate the potential role of chemotactic SDF-1/CXCR4 signaling pathway in the homing of transplanted BMSCs to the injured cochlea after noise-induced hearing loss (NIHL) in a rat model. White noise exposure (110 dB) paradigm was used for hearing loss induction in male rats for 6 hours in 5 days. Distortion-product otoacoustic emission (DPOAE) responses were recorded before the experiment and post noise exposure.Hoechst 33342-labeled BMSCs and CXCR4 antagonist (AMD3100)-treated BMSCs were injected into the rat cochlea through the round window. SDF-1 protein expression in the cochlear tissue was assayed using western blot assay. The number of labeled BMSCs reaching the endolymph was determined after 24 hours.SDF-1 was significantly increased in the cochlear tissue of rats in the noise exposure group than in the control group. The number of Hoechst 33342-labeled BMSCs reaching the endolymph of the cochlea was significantly smaller in the AMD3100-treated BMSCs group than in the normal BMSCs group. Our present findings suggest that the SDF-1/CXCR4 signaling pathway has a critical role in BMSCs migration to the injured cochlea in a rat model of noise-induced hearing loss. Related Articles | Metrics

Select

Injury of the Papez circuit in a patient with traumatic spinal cord injury and concomitant mild traumatic brain injury Sung Ho Jang, Hyeok Gyu Kwon 2018, 13 (1):  161-162.  doi: 10.4103/1673-5374.224384 Abstract ( 143 )   PDF (428KB) ( 375 )   Save Related Articles | Metrics

Select

Neural Regeneration Research: Information for Authors 2018, 13 (1):  163-168.  Abstract ( 111 )   PDF (248KB) ( 240 )   Save Related Articles | Metrics