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15 December 2019, Volume 14 Issue 12 Previous Issue    Next Issue

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Progesterone effects on the oligodendrocyte linage: all roads lead to the progesterone receptor Ignacio Jure,Alejandro F. De Nicola,Florencia Labombarda 2019, 14 (12):  2029-2034.  doi: 10.4103/1673-5374.262570 Abstract ( 126 )   PDF (400KB) ( 166 )   Save A new role has emerged for progesterone after discovering its potent actions away from reproduction in both the central and the peripheral nervous system. The aim of the present report is to discuss progesterone’s mechanisms of action involved in myelination, remyelination and neuroinflammation. The pivotal role of the classic progesterone receptor is described and evidence is compiled about progesterone’s direct effects on oligodendrocyte linage and its indirect effects on oligodendrocyte precursor cell differentiation by decreasing the neuroinflammatory environment. Related Articles | Metrics

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Physiological and pathological effects of amyloid-βspecies in neural stem cell biology Adela Bernabeu-Zornoza, Raquel Coronel, Charlotte Palmer, María Monteagudo, Alberto Zambrano, Isabel Liste 2019, 14 (12):  2035-2042.  doi: 10.4103/1673-5374.262571 Abstract ( 132 )   PDF (356KB) ( 166 )   Save Although amyloid-β peptide is considered neurotoxic, it may mediate several physiological processes during embryonic development and in the adult brain. The pathological function of amyloid-β peptide has been extensively studied due to its implication in Alzheimer’s disease, but its physiological function remains poorly understood. Amyloid-β peptide can be detected in non-aggregated (monomeric) and aggregated (oligomeric and fibrillary) forms. Each form has different cytotoxic and/or physiological properties, so amyloid-β peptide and its role in Alzheimer’s disease need to be studied further. Neural stem cells and neural precursor cells are good tools for the study on neurodegenerative diseases and can provide future therapeutic applications in diseases such as Alzheimer’s disease. In this review, we provide an outline of the effects of amyloid-β peptide, in monomeric and aggregated forms, on the biology of neural stem cells/neural precursor cells, and discuss the controversies. We also describe the possible molecular targets that could be implicated in these effects, especially GSK3β. A better understanding of amyloid-β peptide (both physiological and pathological), and the signaling pathways involved are essential to advance the field of Alzheimer’s disease. Related Articles | Metrics

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The neuro-glial coagulonome: the thrombin receptor and coagulation pathways as major players in neurological diseases Shany G. Gofrit, Efrat Shavit-Stein 2019, 14 (12):  2043-2053.  doi: 10.4103/1673-5374.262568 Abstract ( 120 )   PDF (1058KB) ( 169 )   Save The neuro-glial interface extends far beyond mechanical support alone and includes interactions through coagulation cascade proteins. Here, we systematically review the evidence indicating that synaptic and node of Ranvier glia cell components modulate synaptic transmission and axonal conduction by a coagulation cascade protein system, leading us to propose the concept of the neuro-glial coagulonome. In the peripheral nervous system, the main thrombin receptor protease activated receptor 1 (PAR1) is located on the Schwann microvilli at the node of Ranvier and at the neuromuscular junction. PAR1 activation effects can be both neuroprotective or harmful, depending on thrombin activity levels. Low physiological levels of thrombin induce neuroprotective effects in the Schwann cells which are mediated by the endothelial protein C receptor. High levels of thrombin induce conduction deficits, as found in experimental autoimmune neuritis, the animal model for Guillaine-Barre syndrome. In the central nervous system, PAR1 is located on the peri-synaptic astrocyte end-feet. Its activation by high thrombin levels is involved in the pathology of primary inflammatory brain diseases such as multiple sclerosis, as well as in other central nervous system insults, including trauma, neoplasms, epilepsy and vascular injury. Following activation of PAR1 by high thrombin levels the seizure threshold is lowered. On the other hand, PAR1 activation by lower levels of thrombin in the central nervous system protects against a future ischemic insult. This review presents the known structure and function of the neuro-glial coagulonome, focusing on coagulation, thrombin and PAR1 in a pathway which may be either physiological (neuroprotective) or detrimental in peripheral nervous system and central nervous system diseases. Understanding the neuro-glial coagulonome may open opportunities for novel pharmacological interventions in neurological diseases. Related Articles | Metrics

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From cortex to cord: motor circuit plasticity after spinal cord injury Andrew R. Brown,Marina Martinez 2019, 14 (12):  2054-2062.  doi: 10.4103/1673-5374.262572 Abstract ( 119 )   PDF (1161KB) ( 197 )   Save Spinal cord injury is associated with chronic sensorimotor deficits due to the interruption of ascending and descending tracts between the brain and spinal cord. Functional recovery after anatomically complete spinal cord injury is limited due to the lack of long-distance axonal regeneration of severed fibers in the adult central nervous system. Most spinal cord injuries in humans, however, are anatomically incomplete. Although restorative treatment options for spinal cord injury remain currently limited, research from experimental models of spinal cord injury have revealed a tremendous capability for both spontaneous and treatment-induced plasticity of the corticospinal system that supports functional recovery. We review recent advances in the understanding of corticospinal circuit plasticity after spinal cord injury and concentrate mainly on the hindlimb motor cortex, its corticospinal projections, and the role of spinal mechanisms that support locomotor recovery. First, we discuss plasticity that occurs at the level of motor cortex and the reorganization of cortical movement representations. Next, we explore downstream plasticity in corticospinal projections. We then review the role of spinal mechanisms in locomotor recovery. We conclude with a perspective on harnessing neuroplasticity with therapeutic interventions to promote functional recovery. Related Articles | Metrics

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Turning to myelin turnover Tobias J. Buscham,Maria A. Eichel,Sophie B. Siems,Hauke B. Werner 2019, 14 (12):  2063-2066.  doi: 10.4103/1673-5374.262569 Abstract ( 131 )   PDF (155KB) ( 127 )   Save Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocityIn this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting. Related Articles | Metrics

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Adult neurogenesis and regeneration in zebrafish brain: are the neurotrophins involved in? Pietro Cacialli, Carla Lucini 2019, 14 (12):  2067-2068.  doi: 10.4103/1673-5374.262574 Abstract ( 109 )   PDF (324KB) ( 126 )   Save Neurotrophins (NTs) are implicated in the maintenance and survival of the peripheral and central nervous systems and mediate several forms of synaptic plasticity. Members of the family include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, and NT4. NTs were first identified as survival factors for developing neurons, but are pleiotropic molecules that can exert a variety of functions, including the regulation of neuronal differentiation, axonal and dendritic growth, and synaptic plasticity. NTs interact with two distinct types of receptors: the common p75 neurotrophin receptor, which belongs to the tumor necrosis factor receptor superfamily of death receptors and the Trk receptor tyrosine kinase family. Trks contain an extracellular domain at which the NT binds, a single transmembrane domain, and an intracellular domain with tyrosine kinase activity. Three different Trks have been identified during the vertebrate evolution: TrkA, TrkB, and TrkC. NGF is the preferred ligand for TrkA, BDNF, and NT4/5 are preferred for TrkB, and NT3 for TrkC. Related Articles | Metrics

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G protein-coupled estrogen receptor 1 (GPER) activation triggers different signaling pathways on neurons and astrocytes Cláudio Roque, Graça Baltazar 2019, 14 (12):  2069-2070.  doi: 10.4103/1673-5374.262577 Abstract ( 112 )   PDF (287KB) ( 126 )   Save Estradiol (E2) is the most potent and prevalent form of estrogen, a well-known hormone that regulates multiple tissues and functions in humans. In the brain, E2 regulates processes as diverse as learning, memory, cognition, mood, as well as neurodevelopment and neurodegeneration. The actions of E2 are mediated by classical estrogen receptors (ERs; α and β), and by the G protein-coupled estrogen receptor 1 (GPER or GPR30). Classical ER are predominantly present in the nucleus and cytoplasm, with less than 2% present on the plasma membrane, and mediate genomic cellular effects that occur in the time frame of hours to days. GPER is expressed on the plasma membrane, and on intracellular membranes of the endoplasmic reticulum and Golgi apparatus, and mediates rapid estrogen-induced effects that occur in the time frame of seconds to minutes. Related Articles | Metrics

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Role of formyl peptide receptor 2(FPR2) in the normal brain and in neurological conditions Wei-Yi Ong, John Jia En Chua 2019, 14 (12):  2071-2072.  doi: 10.4103/1673-5374.262575 Abstract ( 160 )   PDF (367KB) ( 151 )   Save There is much recent interest in the role of the anti-inflammatory molecules and their receptors in the normal brain and in neurological disorders. The formyl peptide receptor (FPR) subfamily of G protein-coupled receptors play important roles in these processes. Binding to specific peptides triggers activation of FPRs, leading to signalling events that regulate inflammatory responses. One member of this subfamily of receptors is FPR2, also known as ALX (the lipoxin A4 (LXA4) receptor). FPR2 is specifically activated by LXA4 and resolvin D1 (RvD1). LXA4 is an anti-inflammatory molecule produced by the action of lipoxygenases on arachidonic acid, while RvD1 is produced by the action of lipoxygenases on docosahexaenoic acid, a component of fish oil. Activation of FPR2 by LXA4 or RvD1 triggers downstream signalling cascades, e.g., inhibition of calcium-calmodulin dependent protein kinase and p38 mitogen-activated protein kinase phosphorylation, leading to a reduction in inflammatory responses. Annexin A1 (ANXA1) is another molecule which could interact with FPR2. A Ca 2+ -dependent phospholipid-binding protein, ANXA1 suppresses phospholipase A 2 activity to reduce arachidonic acid and eicosanoid production and decrease leukocyte inflammatory events such as cell migration, chemotaxis, phagocytosis and respiratory burst. While many studies have shown that binding to FPR2 is a chemotactic signal to attract macrophages to the site of tissue injury, other studies have highlighted that it is part of an anti-inflammatory process. For example, from some of the studies detailed below, it seems that activation of this receptor does not itself cause further production of pro-inflammatory mediators by macrophages. Instead, FPR2 appears to attract macrophages and other immune cells to the site of tissue injury to initiate a “quiet mopping-up process”to resolve inflammation. Related Articles | Metrics

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Engineering nerve guidance conduits with three-dimenisonal bioprinting technology for long gap peripheral nerve regeneration Jian Du, Xiaofeng Jia 2019, 14 (12):  2073-2074.  doi: 10.4103/1673-5374.262580 Abstract ( 131 )   PDF (427KB) ( 1064 )   Save Nerve guidance conduits (NGCs) are tubular structures that are used to bridge the gap of a severed nerve, thereby acting as a guide and protective micro-environment for the regenerating axons and as a barrier against the in-growth of scar-forming tissue. In the last few decades, the concept of NGCs has evolved from a research tool to investigate nerve regeneration into a translational product that is now being used clinically as an alternative for autologous nerve graft repair, due to their availability and ease of fabrication. At the moment, various nerve conduits have been approved for clinical use and are being marketed, including Neurotube TM (K983007, 1999), Salubridge TM  (K002098, 2000), NeuraGen TM (K011168, 2001), Surgisis TM Nerve Cuff (K031069, 2003), Neurolac TM (K050573, 2005; K112267, 2011), Cova TM ORTHO-NERVE (K103081, 2012), Reaxon TM Plus (K143711, 2015) (Du et al., 2018a). However, clinical outcomes associated with the use of artificial nerve conduits are often inferior to that of autografts, particularly over long lesion gaps. Although their clinical use has been limited, mainly to the repair of relatively small defects (< 3 cm), such as small-caliber digital nerves, the potential for extending their clinical application to the repair of larger defects and larger mixed or motor nerves has made the development of an ideal nerve tube appealing for both scientists and the medical device industry. Related Articles | Metrics

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MicroRNAs as biomarkers of diabetic retinopathy and disease progression Janez Konc 2019, 14 (12):  2075-2076.  doi: 10.4103/1673-5374.262576 Abstract ( 86 )   PDF (481KB) ( 122 )   Save The development of new drugs is traditionally focused on a single target protein. Only recently has it been recognized that drugs, i.e., small molecules, usually bind to several target proteins and thus have a wider spectrum of different effects. Natural substances are very interesting in this respect, as more than 32% of all drugs on the market today are derived from natural sources. However, natural substances are largely unexplored as their exact mechanisms of action are often unknown. In order to determine their actions, we can resort to computational methods. Computational screening enables the identification of potential target proteins, the explanation of observed effects and the prediction of novel effects of natural compounds. Computer algorithms enable targeted investigations, such as focused experimental tests on a specific target protein or a family of potential target proteins. Recently, we used computational screening to identify new potential target proteins for two natural compounds, curcumin and resveratrol, components of turmeric and grape, respectively. These two compounds have been shown to have anti-neuroinflammatory activity and therapeutic effects in the treatment of neurodegenerative diseases. We identified new  potential target proteins of these two compounds, the modulation of which with resveratrol and curcumin might help to explain their therapeutic effects in neurodegenerative diseases, in particular in the Alzheimer’s disease. We have discovered some already known target proteins and also new potential target proteins involved in neurodegeneration. Consisting of two complementary methods, inverse molecular docking and comparison of protein binding sites, our computational approach is general and can be applied to any natural or synthetic compound. Our results confirm the usefulness of this approach for the determination of new target proteins of natural compounds and for the investigation of their potential effects in the treatment of neurological diseases.   Related Articles | Metrics

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Three-dimensional motion analysis for evaluating motor function in rodents with peripheral nerve injury" Akira Ito, Wang Tianshu, Junichi Tajino 2019, 14 (12):  2077-2078.  doi: 10.4103/1673-5374.262581 Abstract ( 95 )   PDF (513KB) ( 112 )   Save Peripheral nerves act like networks of “wires” that conduct signals from the brain and spinal cord to organs throughout the body. Damage to these nerves leads to numbness, pain, and weakness that eventually reduces the patient’s quality of life. Fortunately, peripheral nerves have a high regenerative capacity and, in most cases, recover from mild disorders and injuries. However, there have been continuous challenges facing the development of treatments for peripheral nerve conditions such as disorders that occur through chronic mechanical stimulation like carpal tunnel syndrome, disorders due to side effects from drugs and intractable diseases like chronic inflammatory demyelinating polyneuropathy. Furthermore, self-regeneration becomes difficult when trauma causes a large gap in the axon, leading to the patient needing nerve transplantation. While autologous nerve transplantation is the current gold standard, only approximately half of the cases obtain satisfactory functional recovery. More endeavors are needed to achieve better therapeutic effect with this treatment method. Related Articles | Metrics

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Glyphosate-based herbicide: a risk factor for demyelinating conditions of the peripheral nervous system? Fabian Szepanowski, Christoph Kleinschnitz, Mark Stettner 2019, 14 (12):  2079-2080.  doi: 10.4103/1673-5374.262579 Abstract ( 147 )   PDF (670KB) ( 141 )   Save Glyphosate is a broad-spectrum herbicide originally introduced to the market in 1974 by the agrochemical company Monsanto. More than 40 years down the line, glyphosate has become one of the most economically meaningful herbicides, with a global use of more than 1.8 million pounds in 2014. In non resistant plants, glyphosate is widely believed to exert its herbicidal effect via inhibition of the 5-enolpyruvylshikimate-3-phosphate synthase, an enzyme of the shikimate pathway required for the biosynthesis of aromatic amino acids in plants and most microorganisms such as fungi, bacteria and some protozoans. As the shikimate pathway has no known physiological function in mammals, glyphosate was considered safe for humans. However, this view has been challenged by several studies conducted by researchers from various fields, leading to the assumption that agricultural spreading of glyphosate might bear health risks, including but not limited to carcinogenic, inflammatory and endocrine disruptive effects. Related Articles | Metrics

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Defective autophagy and Alzheimer’s disease: is calcium the key? Riccardo Filadi, Paola Pizzo 2019, 14 (12):  2081-2082.  doi: 10.4103/1673-5374.262584 Abstract ( 100 )   PDF (675KB) ( 134 )   Save Presenilins and autophagy: Presenilin 1 (PS1) and presenilin 2 (PS2) are homologous, multi-pass transmembrane proteins endowed with pleiotropic functions, ranging from the regulation of membrane trafficking to cell differentiation. Their catalytic activity within the γ-secretase complex, an aspartyl-protease responsible for the intramembrane cleavage of several different type I transmembrane proteins, has been intensively studied in the context of Alzheimer’s disease (AD). Indeed, tens of autosomal dominant mutations in the PSEN1 and PSEN2 genes (encoding PS1 and PS2, respectively) have been associated with the rare familial forms of AD (FAD). FAD-PS1/PS2 mutants are known to alter the γ-secretase-dependent cleavage of the amyloid-precursor-protein, generating amyloid-β (Aβ) peptides, whose toxicity is thought to underlie AD onset and progression. Interestingly, in the last decade, besides their γ-secretase activity, both PS1 and PS2 have been implicated in the regulation of macroautophagy (hereafter called autophagy), a key cellular pathway in which different cell material (proteins, lipids, sugars, damaged organelles) is engulfed within double-membrane vesicles (autophagosomes) and targeted to lysosomes for degradation and recycling of the molecular constituents. Considered that impairment of autophagy can promote neurodegeneration, the finding that FADlinked PSs perturb this process suggests it could be involved in AD pathogenesis. Related Articles | Metrics

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Rethinking to riluzole mechanism of action: the molecular link among protein kinase CK1δ activity, TDP-43 phosphorylation, and amyotrophic lateral sclerosis pharmacological treatment Maicol Bissaro, Stefano Moro 2019, 14 (12):  2083-2085.  doi: 10.4103/1673-5374.262578 Abstract ( 102 )   PDF (949KB) ( 649 )   Save Life expectancy in industrialized and developed countries will continue to increase in the near future. Consequently, over the last years, the incidence and social impact of neurodegenerative diseases have increased, highlighting an urgent need for new and more effective therapeutic strategies to counter these terrible disorders. While we tend to think about neurodegenerative diseases as conditions that are uniquely associated with the elder age, these diseases cover a diverse range across the entire lifespan, even affecting infants and children. Related Articles | Metrics

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Remote photobiomodulation: an emerging strategy for neuroprotection Luke C. Gordon, Daniel M. Johnstone 2019, 14 (12):  2086-2087.  doi: 10.4103/1673-5374.262573 Abstract ( 104 )   PDF (111KB) ( 145 )   Save Photobiomodulation (PBM) - the irradiation of cells or tissues with low-intensity red to near-infrared light - is emerging as an effective means of enhancing cell and tissue resilience and repair. As reviewed elsewhere, the intracellular effects of PBM appear to be primarily mediated by cytochrome C oxidase, a key enzyme in the mitochondrial respiratory chain and a primary photoacceptor of red to near-infrared light. Absorption of light by cytochrome C oxidase alters its redox state, resulting in increased ATP production, the liberation of nitric oxide and a transient burst in reactive oxygen species. This, in turn, triggers a cascade of secondary downstream effects that collectively enhance cell and tissue resilience, including the reactive oxygen species-mediated activation of key transcription factors and consequent effects on the expression of genes involved in cell proliferation and migration and in the production of cytokines and growth factors. In the context of neurodegenerative diseases, the disease-modifying or “neuroprotective” effects of PBM have been demonstrated in animal models of retinal degeneration, stroke, traumatic brain injury, Alzheimer’s disease, frontotemporal dementia and Parkinson’s disease (PD). Related Articles | Metrics

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On the road to new treatments for multiple sclerosis: targeting dendritic cell migration into the central nervous system Megha Meena, Nathalie Cools 2019, 14 (12):  2088-2090.  doi: 10.4103/1673-5374.262583 Abstract ( 92 )   PDF (1113KB) ( 116 )   Save Distinct migratory pathways and trafficking of dendritic cells to the central nervous system (CNS): The immune system is a host defense mechanism protecting against invaders, such as bacteria and viruses, while maintaining tolerance to self. Nonetheless, a few sites throughout the body are believed to be immunologically inert, such as the testes, the eye and the brain. Indeed, experiments in the mid-20 th century gave rise to the concept of the brain as a site of immune privilege. Originally, the immune privilege of the brain was thought to be absolute, attributed by a physical blood-brain barrier (BBB) protecting the CNS from the entry of pathogens and circulating immune cells. These views have changed and currently, the CNS is seen as an immune-specialized site regulated by immunological components into and within the CNS. However, in neuroinflammatory disorders, such as multiple sclerosis (MS), the resident and infiltrating immune cells damage components of the CNS resulting in neurodegeneration. Among the various immune cells that infiltrate the CNS are dendritic cells (DCs), professional antigen-presenting cells capable to initiate both immunity and tolerance. DCs are known to transmigrate into the CNS during neuro-inflammation via different routes, one of them is through the activation and breakdown of the BBB. The infiltration of peripheral DCs in the CNS follow a classical multistep model, which are arbitrated by the expression of chemokine receptors and adhesion molecules on the surface of DCs). Previous findings from our group have demonstrated aberrant expression of migration markers and increased chemotaxis, besides aberrant expression of maturation markers, by circulating DCs of MS patients as compared to DCs from healthy controls. A better understanding of immune cell infiltration, explicitly DC transmigration into the CNS, can provide a better comprehension of the underlying processes driving neuroinflammation, such as in MS, ultimately moving forward the field by identifying new treatment targets. Indeed, although currently available therapeutics can modulate immune cell migration in general, selective hampering of pathogenic DC recruitment into the CNS in particular, might form the basis for the design of new therapeutic strategies for MS. Related Articles | Metrics

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Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders Rodrigo Pacheco 2019, 14 (12):  2091-2092.  doi: 10.4103/1673-5374.262582 Abstract ( 99 )   PDF (979KB) ( 112 )   Save The emerging role of gut microbiota as a key player in the development of neurodegenerative disorders: Mammals have evolved together with commensal microbiota to establish a symbiotic relationship in which they regulate reciprocally by synthesizing and responding to several common chemical substances. In this regard, gut microbiota constitutes a consortium of bacteria that not only participates in the degradation of nutrients, but also produces metabolites, fatty acids and neurotransmitters that can act on the enzymes and receptors expressed in eukaryotic cells, which considerably affects the physiology of the host and contribute to maintaining homeostasis. Related Articles | Metrics

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Interaction between cannabinoid and nucleotide systems as a new mechanism of signaling in retinal cell death Hércules R. Freitas, Ricardo A. M. Reis, Ana L. M. Ventura, Guilherme R. França 2019, 14 (12):  2093-2094.  doi: 10.4103/1673-5374.262585 Abstract ( 101 )   PDF (400KB) ( 105 )   Save Nervous system emerges from complex signaling interactions where extrinsic (neurotransmitters and trophic factors, among others) and intrinsic factors (transcription factors) interplay in the developing tissue to control gene activity promoting chronic changes in cell genesis, migration, differentiation and death. The retinal microenvironment is regulated by a broad variety of chemicals, including endocannabinoids and nucleotides that modulate embryonic progenitor-neuron-Müller glia signaling in very early developing or pathophysiological conditions. Accumulated evidence demonstrate the presence of a functional cannabinoid system in this tissue, with many retina cell types expressing cannabinoid CB1 and/or CB2 receptors, the two main ligands N-arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG) and enzymes that generate N-acyl phosphatidylethanolamine phospholipase, and diacylglycerol lipase (DAGL) and degrade fatty acid amide hydrolase, monoacylglycerol lipase (MAGL) and cyclooxygenase-2 endocannabinoids. As in other areas of the central nervous system, cannabinoids seem to regulate neurotransmission in the retina by inhibiting the release of transmitters such as dopamine, norepinephrine, γ-aminobutyric acid and glutamate. They also play an important role in retinal circuitry and in scotopic vision by modulating Ca 2+ and K + channels in bipolar cells and photoreceptors. Moreover, under pathological conditions, cannabinoids seem to induce neuroprotection in this tissue. Albeit these protective effects, however, recent data are implicating cannabinoid receptors in cell death in the retina, both in the early developing and diseased tissue. Related Articles | Metrics

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Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection Feng Guan,Wei-Cheng Peng,Hui Huang,Zu-Yuan Ren,Zhen-Yu Wang,Ji-Di Fu,Ying-Bin Li,Feng-Qi Cui,Bin Dai,Guang-Tong Zhu,Zhi-Yong Xiao,Bei-Bei Mao,Zhi-Qiang Hu 2019, 14 (12):  2095-2103.  doi: 10.4103/1673-5374.262591 Abstract ( 77 )   PDF (707KB) ( 128 )   Save Cerebral ventricular infection (CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques (NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery (NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I (n = 3), Grade II (n = 13), Grade III (n = 10), and Grade IV (n = 6) CVI. The three patients with grade I CVI underwent one NES, the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two (n = 3) or three (n = 3) NESs. The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures. Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus, 18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6- to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China. Related Articles | Metrics

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Novel circular RNAs expressed in brain microvascular endothelial cells after oxygen-glucose deprivation/recovery Wei Liu,Chao Jia,Li Luo,Hai-Lian Wang,Xiao-Li Min,Jiang-Hui Xu,Li-Qing Ma,Xia-Min Yang,Ying-Wei Wang,Fei-Fei Shang 2019, 14 (12):  2104-2111.  doi: 10.4103/1673-5374.262589 Abstract ( 112 )   PDF (2125KB) ( 184 )   Save Circular RNAs (circRNAs) are generated by head-to-tail splicing and are ubiquitously expressed in all multicellular organisms. Their important biological functions are increasingly recognized. Cerebral ischemia reperfusion injury-induced brain microvascular endothelial cell dysfunction is an initial stage of blood-brain barrier disruption. The expression profile and potential function of circRNAs in brain microvascular endothelial cells is unknown. Rat brain microvascular endothelial cells were extracted and cultured in glucose-free medium for 4 hours with 5% CO2 and 95% N2, and the medium was then replaced with complete growth medium for 6 hours. The RNA in these cells was then extracted. The circRNA was identified by Find_circ and CIRI2 software. Functional and pathway enrichment analysis of genes that were common to differentially expressed mRNAs and circRNA host genes was performed by the Database for Annotation, Visualization and Integrated Discovery Functional Annotation Tool. Miranda software was used to predict microRNAs that were potentially sponged by circRNAs. Furthermore, cytoscape depicted the circR-NA-microRNA interaction network. The results showed that there were 1288 circRNAs in normal and oxygen-glucose deprived/recovered primary brain microvascular endothelial cells. There are 211 upregulated and 326 downregulated differentially expressed circRNAs. The host genes of these differentially expressed circRNAs overlapped with those of differentially expressed mRNAs. The shared genes were further studied by functional enrichment analyses, which revealed that circRNAs may contribute to calcium ion function and the cyclic guanosine 3′,5′-monophosphate (CAMP) dependent protein kinase (PKα) signaling pathway. Next, quantitative reverse transcription polymerase chain reaction assays were performed to detect circRNA levels transcribed from the overlapping host genes. Eight out of the ten circRNAs with the highest fold-change identified by sequencing were successfully verified. Subsequently, the circRNA-microRNA interaction networks of these eight circRNAs were explored by bioinformatic analysis. These results demonstrate that altered circRNAs may be important in the pathogenesis of cerebral ischemia reperfusion injury and consequently may also be potential therapeutic targets for cerebral ischemia diseases. All animal experiments were approved by the Chongqing Medical University Committee on Animal Research, China (approval No. CQMU20180086) on March 22, 2018. Related Articles | Metrics

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N-methyl-D-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice Juan Ding,Chun Zhang,Yi-Wei Zhang, Quan-Rui Ma, Yin-Ming Liu, Tao Sun,Juan Liu 2019, 14 (12):  2112-2117.  doi: 10.4103/1673-5374.262597 Abstract ( 126 )   PDF (2481KB) ( 174 )   Save N-methyl-D-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the N-methyl-D-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the N-methyl-D-aspartate receptor subunit 1 (NR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In N-methyl-D-aspartate-treated mice, N-methyl-D-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of NR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of NR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. N-methyl-D-aspartate could reverse the above changes. These results indicated that NR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting NR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the Ningxia Medical University, China (approval No. 2014-014) on March 6, 2014. Related Articles | Metrics

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Long non-coding RNA GAS5 promotes PC12 cells differentiation into Tuj1-positive neuron-like cells and induces cell cycle arrest He-Yan Zhao, Sheng-Tong Zhang, Xiang Cheng, Hao-Ming Li, Lei Zhang, Hui He, Jian-Bing Qin, Wei-Ye Zhang, Yan Sun, Guo-Hua Jin 2019, 14 (12):  2118-2125.  doi: 10.4103/1673-5374.262592 Abstract ( 108 )   PDF (2452KB) ( 159 )   Save Growth arrest-specific 5 (GAS5) is an anti-oncogene that has been extensively studied in tumors. However, research on GAS5 in the context of nervous system disease is rare at present. This study aimed to investigate the role of the long non-coding RNA GAS5 in rat pheochromocytoma cells (PC12 cells). GAS5-overexpressing lentivirus was transfected into PC12 cells, and expression levels of GAS5 and C-myc were detected by real-time PCR. Ratios of cells in S phase were detected by 5-ethynyl-2′-deoxyuridine. Immunohistochemical staining was used to detect the immunoreactivity of neuron microtubule markers Tuj1, doublecortin, and microtubule-associated protein 2. Apoptosis was detected by flow cytometry, while expression of acetylcholine in cells was detected by western blot assay. We found that GAS5 can promote PC12 cells to differentiate into Tuj1-positive neuron-like cells with longer processes. In addition, cell proliferation and cell cycle were significantly suppressed by GAS5, whereas it had no effect on apoptosis of PC12 cells. Our results indicate that GAS5 could increase the expression of choline acetyltransferase and acetylcholine release. Thus, we speculate that GAS5 is beneficial to the recovery of neurons and the cholinergic nervous system. Related Articles | Metrics

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Modulatory effect of International Standard Scalp Acupuncture on brain activation in the elderly as revealed by resting-state fMRI Wai-Yeung Chung,Song-Yan Liu,Jing-Chun Gao,Yi-Jing Jiang,Jing Zhang,Shan-Shan Qu,Ji-Ping Zhang,Xiao-Long Tan,Jun-Qi Chen,Sheng-Xu Wang 2019, 14 (12):  2126-2131.  doi: 10.4103/1673-5374.262590 Abstract ( 125 )   PDF (776KB) ( 481 )   Save The specific mechanisms by which acupuncture affects the central nervous system are unclear. In the International Standard Scalp Acupuncture system, acupuncture needles are applied at the middle line of the vertex, anterior parietal-temporal oblique line, and the posterior parietal-temporal oblique line. We conducted a single-arm prospective clinical trial in which seven healthy elderly volunteers (three men and four women; 50–70 years old) received International Standard Scalp Acupuncture at MS5 (the mid-sagittal line between Baihui (DU20) and Qianding (DU21)), the left MS6 (line joining Sishencong (EX-HN1) and Xuanli (GB6)), and the left MS7 (line joining DU20 and Qubin (GB7)). After acupuncture, resting-state functional magnetic resonance imaging demonstrated changes in the fractional amplitude of low frequency fluctuations and regional homogeneity in various areas, showing remarkable enhancement of regional homogeneity in the bilateral anterior cingulate, left medial frontal gyrus, supramarginal gyrus, right middle frontal gyrus, and inferior frontal gyrus. Functional connectivity based on a seed region at the right middle frontal gyrus (42, 51, 9) decreased at the bilateral medial superior frontal gyrus. Our data preliminarily indicates that the international standard scalp acupuncture in healthy elderly participants specifcally enhances the correlation between the brain regions involved in cognition and implementation of the brain network regulation system and the surrounding adjacent brain regions. The study was approved by the Ethics Committee of the China-Japan Union Hospital at Jilin University, China, on July 18, 2016 (approval No. 2016ks043). Related Articles | Metrics

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Comparison between direct repair and human acellular nerve allografting during contralateral C7 transfer to the upper trunk for restoration of shoulder abduction and elbow flexion Liang Li,Wen-Ting He,Ben-Gang Qin, Xiao-Lin Liu, Jian-Tao Yang,Li-Qiang Gu 2019, 14 (12):  2132-2140.  doi: 10.4103/1673-5374.262600 Abstract ( 127 )   PDF (4573KB) ( 164 )   Save Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system; meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion. Thus, if direct coaptation is not possible, use of acellular nerve allografts is a suitable option. This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Sun Yat-sen University, China (Application ID: [2017] 290) on November 14, 2017. Related Articles | Metrics

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Differentiating between Alzheimer’s disease, amnestic mild cognitive impairment, and normal aging via diffusion kurtosis imaging Guo-Ping Song,Ting-Ting Yao,Dan Wang, Yue-Hua Li 2019, 14 (12):  2141-2146.  doi: 10.4103/1673-5374.262594 Abstract ( 124 )   PDF (1830KB) ( 157 )   Save Diffusion kurtosis imaging can be used to assess pathophysiological changes in tissue structure and to diagnose central nervous system diseases. However, its sensitivity in assessing hippocampal differences between patients with Alzheimer’s disease and those with amnestic mild cognitive impairment has not been characterized. Here, we examined 20 individuals with Alzheimer’s disease (11 men and 9 women, mean 73.2 ± 4.49 years), 20 with amnestic mild cognitive impairment (10 men and 10 women, mean 71.55 ± 4.77 years), and 20 normal controls (11 men and 9 women, mean 70.45 ± 5.04 years). We conducted diffusion kurtosis imaging, using a 3.0 T magnetic resonance scanner, to compare hippocampal differences among the three groups. The results demonstrated that the right hippocampal volume and bilateral mean kurtosis were remarkably smaller in individuals with Alzheimer’s disease compared with those with amnestic mild cognitive impairment and normal controls. Further, the mean kurtosis was lower in the amnestic mild cognitive impairment group compared with the normal control group. The mean diffusion in the left hippocampus was lower in the Alzheimer’s disease group than in the amnestic mild cognitive impairment and normal control groups, while the mean diffusion in the right hippocampus was lower in the Alzheimer’s disease group than in the normal control group. Fractional anisotropy was similar among the three groups. These results verify that bilateral mean kurtosis and mean diffusion are sensitive to the diagnosis of Alzheimer’s disease and amnestic mild cognitive impairment. This study was approved by the Ethics Review Board of Affiliated Sixth People’s Hospital of Shanghai Jiao Tong University, China on May 4, 2010 (approval No. 2010(C)-6). Related Articles | Metrics

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Optogenetics-induced activation of glutamate receptors improves memory function in mice with Alzheimer’s disease Ke-Wei Wang,Xiao-Lin Ye,Ting Huang,Xi-Fei Yang,Liang-Yu Zou 2019, 14 (12):  2147-2155.  doi: 10.4103/1673-5374.262593 Abstract ( 130 )   PDF (2437KB) ( 144 )   Save Optogenetics is a combination of optics and genetics technology that can be used to activate or inhibit specific cells in tissues. It has been used to treat Parkinson’s disease, epilepsy and neurological diseases, but rarely Alzheimer’s disease. Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1–42 peptide (Aβ1–42). Subsequently, the region was stimulated with a 473 nm laser (1–3 ms, 10 Hz, 5 minutes). The novel object recognition test was conducted to test memory function in mice. Immunohistochemical staining was performed to analyze the numbers of NeuN and synapsin Ia/b-positive cells in the hippocampus. Western blot assay was carried out to analyze the expression levels of glial fibrillary acidic protein, NeuN, synapsin Ia/b, metabotropic glutamate receptor-1a (mGluR-1a), mGluR-5, N-methyl-D-aspartate receptor subunit NR1, glutamate receptor 2, interleukin-1β, interleukin-6 and interleukin-10. Optogenetic stimulation improved working and short-term memory in mice with Alzheimer’s disease. This neuroprotective effect was associated with increased expression of NR1, glutamate receptor 2 and mGluR-5 in the hippocampus, and decreased expression of glial fibrillary acidic protein and interleukin-6. Our results show that optogenetics can be used to regulate the neuronal-glial network to ameliorate memory functions in mice with Alzheimer’s disease. The study was approved by the Animal Resources Committee of Jinan University, China (approval No. LL-KT-2011134) on February 28, 2011. Related Articles | Metrics

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Relationship between high dietary fat intake and Parkinson’s disease risk: a meta-analysis Yan Qu,Xi Chen,Man-Man Xu,Qiang Sun 2019, 14 (12):  2156-2163.  doi: 10.4103/1673-5374.262599 Abstract ( 100 )   PDF (1158KB) ( 151 )   Save OBJECTIVE: To assess whether dietary fat intake influences Parkinson’s disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used: (“Paralysis agitans” OR “Parkinson disease” OR “Parkinson” OR “Parkinson’s” OR “Parkinson’s disease”) AND (“fat” OR “dietary fat” OR “dietary fat intake”). DATA SELECTION: Included studies were those with both dietary fat intake and Parkinson’s disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. OUTCOME MEASURES: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson’s disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson’s disease risk. RESULTS: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson’s disease (P = 0.000, odds ratio (OR) = 1.49, 95% confidence interval (CI): 1.26–1.75); in contrast, high total fat intake was not associated with Parkinson’s disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91–1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88–1.20) reduced the risk of Parkinson’s disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97–1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92–1.29) both increased the risk of Parkinson’s disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73–1.05), α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72–1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75–1.06) were all linked with a trend toward reduced Parkinson’s disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91–1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96–1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94–1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87–1.18) intake was not associated with Parkinson’s disease. CONCLUSION: Dietary fat intake affects Parkinson’s disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson’s disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson’s disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson’s disease. Related Articles | Metrics

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Axonotmesis-evoked plantar vasodilatation as a novel assessment of C-fiber afferent function after sciatic nerve injury in rats Xue-Song Wang,Xue Chen,Tian-Wen Gu,Ya-Xian Wang,Da-Guo Mi,Wen Hu 2019, 14 (12):  2164-2172.  doi: 10.4103/1673-5374.262595 Abstract ( 98 )   PDF (2422KB) ( 152 )   Save Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups; whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013. Related Articles | Metrics

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Application of custom anatomy-based nerve conduits on rabbit sciatic nerve defects: in vitro and in vivo evaluations Yamuhanmode·Alike,Maimaiaili·Yushan,Ajimu·Keremu,Alimujiang·Abulaiti,Zhen-Hui Liu,Wei Fu,Li-Wei Yan,Aihemaitijiang·Yusufu,Qing-Tang Zhu 2019, 14 (12):  2173-2182.  doi: 10.4103/1673-5374.262601 Abstract ( 130 )   PDF (6099KB) ( 196 )   Save The intermingling of regenerated nerve fibers inside nerve grafts is the main reason for mismatched nerve fibers. This is one of the key factors affecting limb function recovery after nerve injury. Previous research has shown that the accuracy of axon regeneration can be improved by a bionic structural implant. To this aim, iodine and freeze-drying high-resolution micro-computed tomography was performed to visualize the 3D topography of the New Zealand rabbit sciatic nerve (25 mm). A series of 1-, 2-, 3-, and 4-custom anatomy-based nerve conduits (CANCs) were fabricated based on the anatomical structure of the nerve fascicle. The match index, luminal surface, and mechanical properties of CANCs were evaluated before implanting in a 10-mm gap of the sciatic nerve. Recovery was evaluated by histomorphometric analyses, electrophysiological study, gastrocnemius muscle weight recovery ratio, and behavioral assessments at 12 and 24 weeks postoperatively. The accuracy of nerve regeneration was determined by changes in fluorescence-labeled profile number during simultaneous retrograde tracing. Our results showed that the optimal preprocessing condition for high-resolution micro-computed tomography visualization was treatment of the sciatic nerve with 40% Lugol’s solution for 3 days followed by lyophilization for 2 days. In vitro experiments demonstrated that the match index was highest in the 3-CANC group, followed by the 2-, 1-, and 4-CANC groups. The luminal surface was lowest in the 1-CANC group. Mechanical properties (transverse compressive and bending properties) were higher in the 3-and 4-CANC groups than in the 1-CANC group. In vivo experiments demonstrated that the recovery (morphology of regenerated fibers, compound muscle action potential, gastrocnemius muscle weight recovery ratio, pain-related autotomy behaviors, and range of motion) in the 3-CANC group was superior to the other CANC groups, and achieved the same therapeutic effect as the autograft. The simultaneous retrograde tracing results showed that the percentages of double-labeled profiles of the 2-, 3-, and 4-CANC groups were comparatively lower than that of the 1-CANC group, which indicates that regenerated nerve fascicles were less intermingled in the 2-, 3-, and 4-CANC groups. These findings demonstrate that the visualization of the rabbit sciatic nerve can be achieved by iodine and freeze-drying high-resolution micro-computed tomography, and that this method can be used to design CANCs with different channels that are based on the anatomical structure of the nerve. Compared with the 1-CANC, 3-CANC had a higher match index and luminal surface, and improved the accuracy of nerve regeneration by limiting the intermingling of the regenerated fascicles. All procedures were approved by the Animal Care and Use Committee, Xinjiang Medical University, China on April 4, 2017 (ethics approval No. IACUC20170315-02). Related Articles | Metrics

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Differential gene and protein expression between rat tibial nerve and common peroneal nerve during Wallerian degeneration Yao-Fa Lin,Zheng Xie,Jun Zhou,Gang Yin,Hao-Dong Lin 2019, 14 (12):  2183-2191.  doi: 10.4103/1673-5374.262602 Abstract ( 108 )   PDF (3594KB) ( 172 )   Save Wallerian degeneration and nerve regeneration after injury are complex processes involving many genes, proteins and cytokines. After different peripheral nerve injuries the regeneration rate can differ. Whether this is caused by differential expression of genes and proteins during Wallerian degeneration remains unclear. The right tibial nerve and the common peroneal nerve of the same rat were exposed and completely cut through and then sutured in the same horizontal plane. On days 1, 7, 14, and 21 after surgery, 1–2 cm of nerve tissue distal to the suture site was dissected out from the tibial and common peroneal nerves. The differences in gene and protein expression during Wallerian degeneration of the injured nerves were then studied by RNA sequencing and proteomic techniques. In the tibial and common peroneal nerves, there were 1718, 1374, 1187, and 2195 differentially expressed genes, and 477, 447, 619, and 495 differentially expressed proteins on days 1, 7, 14, and 21 after surgery, respectively. Forty-seven pathways were activated during Wallerian degeneration. Three genes showing significant differential expression by RNA sequencing (Hoxd4, Lpcat4 and Tbx1) were assayed by real-time quantitative polymerase chain reaction. RNA sequencing and real-time quantitative polymerase chain reaction results were consistent. Our findings showed that expression of genes and proteins in injured tibial and the common peroneal nerves were significantly different during Wallerian degeneration at different time points. This suggests that the biological processes during Wallerian degeneration are different in different peripheral nerves after injury. The procedure was approved by the Animal Experimental Ethics Committee of the Second Military Medical University, China (approval No. CZ20160218) on February 18, 2016. Related Articles | Metrics

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CNB-001 reduces paraplegia in rabbits following spinal cord ischemia Paul A. Lapchak,Paul D. Boitano,Rene Bombien,Daisy Chou,Margot Knight,Anja Muehle,Mihaela Te Winkel,Ali Khoynezhad 2019, 14 (12):  2192-2198.  doi: 10.4103/1673-5374.262598 Abstract ( 96 )   PDF (572KB) ( 534 )   Save Spinal cord ischemia associated with trauma and surgical procedures including thoraco-abdominal aortic aneurysm repair and thoracic endovascular aortic repair results in devastating clinical deficits in patients. Because spinal cord ischemia is inadequately treated, we studied the effects of [4-((1E)-2-(5-(4-hydroxy-3-methoxystyryl-)-1-phenyl-1H-pyrazoyl-3-yl) vinyl)-2-methoxy-phenol)] (CNB-001), a novel curcumin-based compound, in a rabbit SCI model. CNB-001 is known to inhibit human 5-lipoxygenase and 15-lipoxygenase and reduce the ischemia-induced inflammatory response. Moreover, CNB-001 can reduce the level of oxidative stress markers and potentiate brain-derived neurotrophic factor and brain-derived neurotrophic factor receptor signaling. The Tarlov scale and quantal analysis technique results revealed that CNB-001 administered as an intravenous dose (bolus) 30 minutes prior to spinal cord ischemia improved the behaviors of female New Zealand White rabbits. The improvements were similar to those produced by the uncompetitive N-methyl-D-aspartate receptor antagonist memantine. At 48 hours after aortic occlusion, there was a 42.7% increase (P < 0.05) in tolerated ischemia duration (n = 14) for rabbits treated with CNB-001 (n = 16), and a 72.3% increase for rabbits treated with the positive control memantine (P < 0.05) (n = 23) compared to vehicle-treated ischemic rabbits (n = 22). CNB-001 is a potential important novel treatment for spinal cord ischemia induced by aortic occlusion. All experiments were approved by the CSMC Institutional Animal Care and Use Committee (IACUC #4311) on November 1, 2012. Related Articles | Metrics

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Fresh human amniotic membrane effectively promotes the repair of injured common peroneal nerve Zhong-Yuan Zhang,Jin Yang,Zhen-Hai Fan,Da-Li Wang,Yu-Ying Wang,Tao Zhang,Li-Mei Yu,Chang-Yin Yu 2019, 14 (12):  2199-2208.  doi: 10.4103/1673-5374.262596 Abstract ( 131 )   PDF (3959KB) ( 146 )   Save Suture and autologous nerve transplantation are the primary therapeutic measures for completely severed nerves. However, imbalances in the microenvironment and adhesion of surrounding tissues can affect the quality of nerve regeneration and repair. Previous studies have shown that human amniotic membrane can promote the healing of a variety of tissues. In this study, the right common peroneal nerve underwent a 5-mm transection in rats. Epineural nerve repair was performed using 10/0 non-absorbable surgical suture. The repair site was wrapped with a two-layer amniotic membrane with α-cyanoacrylate rapid medical adhesive after suture. Hindlimb motor function was assessed using footprint analysis. Conduction velocity of the common peroneal nerve was calculated by neural electrical stimulation. The retrograde axoplasmic transport of the common peroneal nerve was observed using fast blue BB salt retrograde fluorescent staining. Hematoxylin-eosin staining was used to detect the pathological changes of the common peroneal nerve sputum. The mRNA expression of axon regeneration-related neurotrophic factors and inhibitors was measured using real-time polymerase chain reaction. The results showed that the amniotic membrane significantly improved the function of the injured nerve; the toe spread function rapidly recovered, the nerve conduction velocity was restored, and the number of fast blue BB salt particles were increased in the spinal cord. The amniotic membrane also increased the recovery rate of the tibialis anterior muscle and improved the tissue structure of the muscle. Meanwhile, mRNA expression of nerve growth factor, growth associated protein-43, collapsin response mediator protein-2, and brain-derived neurotrophic factor recovered to near-normal levels, while Lingo-1 mRNA expression decreased significantly in spinal cord tissues. mRNA expression of glial-derived neurotrophic factor did not change significantly. Changes in mRNA levels were more significant in amniotic-membrane-wrapping-treated rats compared with model and nerve sutured rats. These results demonstrate that fresh amniotic membrane wrapping can promote the functional recovery of sutured common peroneal nerve via regulation of expression levels of neurotrophic factors and inhibitors associated with axonal regeneration. The study was approved by the Committee on Animal Research and Ethics at the Affiliate Hospital of Zunyi Medical University, China (approval No. 112) on December 1, 2017. Related Articles | Metrics