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Axonal injury

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https://www.readbyqxmd.com/read/28641113/enhanced-functional-genomic-screening-identifies-novel-mediators-of-dual-leucine-zipper-kinase-dependent-injury-signaling-in-neurons
#1
Derek S Welsbie, Katherine L Mitchell, Vinod Jaskula-Ranga, Valentin M Sluch, Zhiyong Yang, Jessica Kim, Eugen Buehler, Amit Patel, Scott E Martin, Ping-Wu Zhang, Yan Ge, Yukan Duan, John Fuller, Byung-Jin Kim, Eman Hamed, Xitiz Chamling, Lei Lei, Iain D C Fraser, Ze'ev A Ronai, Cynthia A Berlinicke, Donald J Zack
Dual leucine zipper kinase (DLK) has been implicated in cell death signaling secondary to axonal damage in retinal ganglion cells (RGCs) and other neurons. To better understand the pathway through which DLK acts, we developed enhanced functional genomic screens in primary RGCs, including use of arrayed, whole-genome, small interfering RNA libraries. Explaining why DLK inhibition is only partially protective, we identify leucine zipper kinase (LZK) as cooperating with DLK to activate downstream signaling and cell death in RGCs, including in a mouse model of optic nerve injury, and show that the same pathway is active in human stem cell-derived RGCs...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28634442/mild-traumatic-brain-injury-evokes-pyramidal-neuron-axon-initial-segment-plasticity-and-diffuse-presynaptic-inhibitory-terminal-loss
#2
Michal Vascak, Jianli Sun, Matthew Baer, Kimberle M Jacobs, John T Povlishock
The axon initial segment (AIS) is the site of action potential (AP) initiation, thus a crucial regulator of neuronal activity. In excitatory pyramidal neurons, the high density of voltage-gated sodium channels (NaV1.6) at the distal AIS regulates AP initiation. A surrogate AIS marker, ankyrin-G (ankG) is a structural protein regulating neuronal functional via clustering voltage-gated ion channels. In neuronal circuits, changes in presynaptic input can alter postsynaptic output via AIS structural-functional plasticity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28632137/electrospun-silk-polyaniline-conduits-for-functional-nerve-regeneration-in-rat-sciatic-nerve-injury-model
#3
Suradip Das, Manav Sharma, Dhiren Saharia, Kushal Sarma, Elizabeth Muir, Utpal Bora
The present study describes the fabrication of polyaniline-silk fibroin nanocomposite based nerve conduits and its subsequent implantation in a rat sciatic nerve injury model for peripheral nerve regeneration. This is the first in vivo study of polyaniline based nerve conduit describing the safety and efficacy of the conduits in treating peripheral nerve injuries. The nanocomposite was synthesised by electrospinning a mixture of silk fibroin protein and polyaniline wherein the silk nanofibers were observed to be uniformly coated with polyaniline nanoparticles...
June 20, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28631619/modeling-trans-spinal-direct-current-stimulation-for-the-modulation-of-the-lumbar-spinal-motor-pathways
#4
Alexander Kuck, Dick Stegeman, Edwin van Asseldonk
OBJECTIVE: Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects. We seek to understand the acute effect of tsDCS, including the generated electric field (EF) and its polarization effect on the spinal circuits, to determine a cellular target...
June 20, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28630333/boosting-cns-axon-regeneration-by-harnessing-antagonistic-effects-of-gsk3-activity
#5
Marco Leibinger, Anastasia Andreadaki, Renate Golla, Evgeny Levin, Alexander M Hilla, Heike Diekmann, Dietmar Fischer
Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3(S/A) knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#6
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28629158/contribution-of-the-degeneration-of-the-neuro-axonal-unit-to-the-pathogenesis-of-multiple-sclerosis
#7
REVIEW
Hannah E Salapa, Sangmin Lee, Yoojin Shin, Michael C Levin
Multiple sclerosis (MS) is a demyelinating, autoimmune disease of the central nervous system. In recent years, it has become more evident that neurodegeneration, including neuronal damage and axonal injury, underlies permanent disability in MS. This manuscript reviews some of the mechanisms that could be responsible for neurodegeneration and axonal damage in MS and highlights the potential role that dysfunctional heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and antibodies to hnRNP A1 may play in MS pathogenesis...
June 18, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#8
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627942/diffusion-imaging-of-mild-traumatic-brain-injury-in-the-impact-accelerated-rodent-model-a-pilot-study
#9
Zora Kikinis, Marc Muehlmann, Ofer Pasternak, Sharon Peled, Praveen Kulkarni, Craig Ferris, Sylvain Bouix, Yogesh Rathi, Inga K Koerte, Steve Pieper, Alexander Yarmarkovich, Caryn L Porter, Bruce S Kristal, Martha E Shenton
PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls...
June 19, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#10
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28625420/formation-and-remodeling-of-the-brain-extracellular-matrix-in-neural-plasticity-roles-of-chondroitin-sulfate-and-hyaluronan
#11
REVIEW
Shinji Miyata, Hiroshi Kitagawa
BACKGROUND: The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624802/heparin-based-coacervate-of-bfgf-facilitates-peripheral-nerve-regeneration-by-inhibiting-endoplasmic-reticulum-stress-following-sciatic-nerve-injury
#12
Rui Li, Shuang Zou, Yanqing Wu, Yiyang Li, Sinan Khor, Yuqin Mao, Huacheng He, Ke Xu, Hongyu Zhang, Xiaokun Li, Jian Wang, Huai Jiang, Qike Jin, Qingsong Ye, Zhouguang Wang, Jian Xiao
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624616/age-related-plasticity-of-the-axon-initial-segment-of-cortical-pyramidal-cells-in-marmoset-monkeys
#13
Nafiseh Atapour, Marcello G P Rosa
Structural plasticity of the axon initial segment (AIS), the site of action potential initiation, is observed as part of the normal early development of the cortex, as well as in association with injury and disease. Here, we show that structural AIS plasticity also occurs with normal aging in adult marmosets. Immunohistochemical techniques were used to reveal the extent of the AIS of layer 2/3A pyramidal cells in 8 neocortical areas. We found that the AIS length varied significantly between areas in young adult (2-3 years old) marmosets, with neurons in frontal area 14C having the longest AIS, and those in the primary visual cortex the shortest...
May 22, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28622711/curcumin-accelerates-the-repair-of-sciatic-nerve-injury-in-rats-through-reducing-schwann-cells-apoptosis-and-promoting-myelinization
#14
Zhiwei Zhao, Xiaoling Li, Qing Li
BACKGROUND: Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. OBJECTIVE: The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. METHODS: After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days...
June 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621704/sensitization-of-trpv1-and-trpa1-via-peripheral-mglur5-signaling-contributes-to-thermal-and-mechanical-hypersensitivity
#15
Kuniya Honda, Masamichi Shinoda, Masahiro Kondo, Kohei Shimizu, Hisashi Yonemoto, Katsuhiko Otsuki, Ryuta Akasaka, Akihiko Furukawa, Koichi Iwata
Peripheral tissue inflammation or injury causes glutamate release from nociceptive axons, keratinocytes and Schwann cells, resulting in thermal hypersensitivity. However, the detailed molecular mechanisms underlying glutamate-induced thermal hypersensitivity are unknown. The aim of this study was to clarify the involvement of peripheral transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) and protein kinase C epsilon (PKCε) in glutamate-induced pain hypersensitivity. The amount of glutamate in the facial tissue was significantly increased 3 days after facial CFA injection...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28621171/boundary-cap-neural-crest-stem-cell-transplants-contribute-mts1-s100a4-expressing-cells-in-the-glial-scar
#16
Carl Trolle, Patrik Ivert, Jan Hoeber, Iris Rocamonde-Lago, Svitlana Vasylovska, Eugen Lukanidin, Elena N Kozlova
AIM: During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury. MATERIALS & METHODS: Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28620418/the-changes-in-rats-with-sciatic-nerve-crush-injury-supplemented-with-evening-primrose-oil-behavioural-morphologic-and-morphometric-analysis
#17
Danial Ramli, Izzuddin Aziz, Masro Mohamad, Dauda Abdulahi, Junedah Sanusi
Nerve crush injuries are commonly used models for axonotmesis to examine peripheral nerve regeneration. As evening primrose oil (EPO) is rich in omega-6 essential fatty acid component and gamma-linolenic acid, studies have shown the potential role of EPO in myelination. Seventy-two healthy adult Sprague-Dawley rats were classified into three groups: normal group, control group, and experimental group. The result indicates that there was significant difference in toe-spreading reflex between the normal and the control groups (1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28620277/accumulating-evidence-for-axonal-translation-in-neuronal-homeostasis
#18
REVIEW
Emily L Spaulding, Robert W Burgess
The specialized structure of the neuron requires that homeostasis is sustained over the meter or more that may separate a cell body from its axonal terminus. Given this impressive distance and an axonal volume that is many times that of the cell body, how is such a compartment grown during development, re-grown after injury, and maintained throughout adulthood? While early answers to these questions focused on the local environment or the cell soma as supplying the needs of the axon, it is now well-established that the axon has some unique needs that can only be met from within...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28616040/stem-cell-transplantation-for-spinal-cord-injury-a-meta-analysis-of-treatment-effectiveness-and-safety
#19
Xiao Fan, Jin-Zhao Wang, Xiao-Min Lin, Li Zhang
OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of stem cell transplantation for spinal cord injury (SCI). DATA SOURCES: PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, Wanfang, and SinoMed databases were systematically searched by computer to select clinical randomized controlled trials using stem cell transplantation to treat SCI, published between each database initiation and July 2016...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28616031/polyethylene-glycol-restores-axonal-conduction-after-corpus-callosum-transection
#20
Ravinder Bamba, D Colton Riley, Richard B Boyer, Alonda C Pollins, R Bruce Shack, Wesley P Thayer
Polyethylene glycol (PEG) has been shown to restore axonal continuity after peripheral nerve transection in animal models. We hypothesized that PEG can also restore axonal continuity in the central nervous system. In this current experiment, coronal sectioning of the brains of Sprague-Dawley rats was performed after animal sacrifice. 3Brain high-resolution microelectrode arrays (MEA) were used to measure mean firing rate (MFR) and peak amplitude across the corpus callosum of the ex-vivo brain slices. The corpus callosum was subsequently transected and repeated measurements were performed...
May 2017: Neural Regeneration Research
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